TY  - JOUR
AB  - BACKGROUND: Coinciding with the SARS-CoV-2 pandemic, malaria cases and malaria-related deaths increased globally between 2020 and 2022. However, evidence linking the pandemic to increased malaria burden remains ambiguous. We assessed the extent to which an observed malaria resurgence in Lambaréné, Gabon, can be associated with pandemic-related disruptions in malaria control programmes. METHODS: Using observational data from two tertiary referral hospitals, spanning 2018 to early 2023, we applied autoregressive integrated moving average (ARIMA) models in an interrupted time series (ITS) framework to test for changes in trends and levels following the onset of the pandemic. The primary outcome is the monthly malaria diagnosis rate (per 1000 all-cause hospital diagnoses). As a sub-analysis, we focused on monthly maternal malaria incidence. RESULTS: Following an initial drop (-47.32, P = 0.031), potentially due to risk-averse behaviours, the malaria diagnosis rate gradually and concavely increased (linear term: 7.32, P = 0.001; squared term: -0.19, P = 0.001) to a peak above pre-pandemic levels. Additional analyses suggest that this resurgence was likely driven by disruptions to malaria control activities and a waning efficacy of malaria control tools administered pre-pandemic. Conversely, a resurgence in maternal malaria incidence was not estimated. CONCLUSION: Findings align with several national and global descriptive reports, but add a more detailed understanding of underlying dynamics, therefore reinforcing the importance of maintaining malaria control in the general population. The absence of a meaningful increase in maternal malaria provides some reassurance that malaria in pregnancy-specific control remained unchanged during the SARS-CoV-2 pandemic. However, observed peaks in post-pandemic maternal malaria incidence should raise concerns given the risks that malaria poses to this group.
AU  - Roeder, F.*
AU  - Adegnika, O.S.*
AU  - Honkpehedji, Y.J.*
AU  - Huth, M.
AU  - Lell, B.*
AU  - Adegnika, A.A.*
AU  - Lopes-Rafegas, I.*
AU  - Sicuri, E.*
C1  - 75527
C2  - 58026
CY  - Great Clarendon St, Oxford Ox2 6dp, England
TI  - Malaria amidst the COVID-19 pandemic in Gabon: An application of autoregressive integrated moving average (ARIMA) models within an interrupted time series (ITS) framework to hospital-based data.
JO  - Int. J. Epidemiol.
VL  - 54
IS  - 5
PB  - Oxford Univ Press
PY  - 2025
SN  - 0300-5771
ER  - 

TY  - JOUR
AB  - BACKGROUND: Model-estimated air pollution exposure products have been widely used in epidemiological studies to assess the health risks of particulate matter with diameters of ≤2.5 µm (PM2.5). However, few studies have assessed the disparities in health effects between model-estimated and station-observed PM2.5 exposures. METHODS: We collected daily all-cause, respiratory and cardiovascular mortality data in 347 cities across 15 countries and regions worldwide based on the Multi-City Multi-Country collaborative research network. The station-observed PM2.5 data were obtained from official monitoring stations. The model-estimated global PM2.5 product was developed using a machine-learning approach. The associations between daily exposure to PM2.5 and mortality were evaluated using a two-stage analytical approach. RESULTS: We included 15.8 million all-cause, 1.5 million respiratory and 4.5 million cardiovascular deaths from 2000 to 2018. Short-term exposure to PM2.5 was associated with a relative risk increase (RRI) of mortality from both station-observed and model-estimated exposures. Every 10-μg/m3 increase in the 2-day moving average PM2.5 was associated with overall RRIs of 0.67% (95% CI: 0.49 to 0.85), 0.68% (95% CI: -0.03 to 1.39) and 0.45% (95% CI: 0.08 to 0.82) for all-cause, respiratory, and cardiovascular mortality based on station-observed PM2.5 and RRIs of 0.87% (95% CI: 0.68 to 1.06), 0.81% (95% CI: 0.08 to 1.55) and 0.71% (95% CI: 0.32 to 1.09) based on model-estimated exposure, respectively. CONCLUSIONS: Mortality risks associated with daily PM2.5 exposure were consistent for both station-observed and model-estimated exposures, suggesting the reliability and potential applicability of the global PM2.5 product in epidemiological studies.
AU  - Yu, W.*
AU  - Huang, W.*
AU  - Gasparrini, A.*
AU  - Sera, F.*
AU  - Schneider, A.E.
AU  - Breitner-Busch, S.
AU  - Kyselý, J.*
AU  - Schwartz, J.*
AU  - Madureira, J.*
AU  - Gaio, V.*
AU  - Guo, Y.L.*
AU  - Xu, R.*
AU  - Chen, G.*
AU  - Yang, Z.*
AU  - Wen, B.*
AU  - Wu, Y.*
AU  - Zanobetti, A.*
AU  - Kan, H.*
AU  - Song, J.*
AU  - Li, S.*
AU  - Guo, Y.*
C1  - 70655
C2  - 55807
CY  - Great Clarendon St, Oxford Ox2 6dp, England
TI  - Ambient fine particulate matter and daily mortality: A comparative analysis of observed and estimated exposure in 347 cities.
JO  - Int. J. Epidemiol.
VL  - 53
IS  - 3
PB  - Oxford Univ Press
PY  - 2024
SN  - 0300-5771
ER  - 

TY  - JOUR
AB  - OBJECTIVES: Observational analyses suggest that high bone mineral density (BMD) is a risk factor for osteoarthritis (OA); it is unclear whether this represents a causal effect or shared aetiology and whether these relationships are body mass index (BMI)-independent. We performed bidirectional Mendelian randomization (MR) to uncover the causal pathways between BMD, BMI and OA. METHODS: One-sample (1S)MR estimates were generated by two-stage least-squares regression. Unweighted allele scores instrumented each exposure. Two-sample (2S)MR estimates were generated using inverse-variance weighted random-effects meta-analysis. Multivariable MR (MVMR), including BMD and BMI instruments in the same model, determined the BMI-independent causal pathway from BMD to OA. Latent causal variable (LCV) analysis, using weight-adjusted femoral neck (FN)-BMD and hip/knee OA summary statistics, determined whether genetic correlation explained the causal effect of BMD on OA. RESULTS: 1SMR provided strong evidence for a causal effect of BMD estimated from heel ultrasound (eBMD) on hip and knee OA {odds ratio [OR]hip = 1.28 [95% confidence interval (CI) = 1.05, 1.57], p = 0.02, ORknee = 1.40 [95% CI = 1.20, 1.63], p = 3 × 10-5, OR per standard deviation [SD] increase}. 2SMR effect sizes were consistent in direction. Results suggested that the causal pathways between eBMD and OA were bidirectional (βhip = 1.10 [95% CI = 0.36, 1.84], p = 0.003, βknee = 4.16 [95% CI = 2.74, 5.57], p = 8 × 10-9, β = SD increase per doubling in risk). MVMR identified a BMI-independent causal pathway between eBMD and hip/knee OA. LCV suggested that genetic correlation (i.e. shared genetic aetiology) did not fully explain the causal effects of BMD on hip/knee OA. CONCLUSIONS: These results provide evidence for a BMI-independent causal effect of eBMD on OA. Despite evidence of bidirectional effects, the effect of BMD on OA did not appear to be fully explained by shared genetic aetiology, suggesting a direct action of bone on joint deterioration.
AU  - Hartley, A.*
AU  - Sanderson, E.*
AU  - Granell, R.*
AU  - Paternoster, L.*
AU  - Zheng, J.*
AU  - Smith, G.D.*
AU  - Southam, L.
AU  - Hatzikotoulas, K.
AU  - Boer, C.G.*
AU  - van Meurs, J.*
AU  - Zeggini, E.
AU  - Genetics of Osteoarthritis Consortium*
AU  - Gregson, C.L.*
AU  - Tobias, J.H.*
C1  - 63774
C2  - 51753
TI  - Using multivariable Mendelian randomization to estimate the causal effect of bone mineral density on osteoarthritis risk, independently of body mass index.
JO  - Int. J. Epidemiol.
PY  - 2021
SN  - 0300-5771
ER  - 

TY  - JOUR
AB  - Background: Although high-density lipoprotein (HDL) and non-HDL cholesterol have opposite associations with coronary heart disease, multi-country reports of lipid trends only use total cholesterol (TC). Our aim was to compare trends in total, HDL and nonHDL cholesterol and the total-to-HDL cholesterol ratio in Asian and Western countries.Methods: We pooled 458 population-based studies with 82.1 million participants in 23 Asian and Western countries. We estimated changes in mean total, HDL and non-HDL cholesterol and mean total-to-HDL cholesterol ratio by country, sex and age group.Results: Since similar to 1980, mean TC increased in Asian countries. In Japan and South Korea, the TC rise was due to rising HDL cholesterol, which increased by up to 0.17 mmol/L per decade in Japanese women; in China, it was due to rising non-HDL cholesterol. TC declined in Western countries, except in Polish men. The decline was largest in Finland and Norway, at similar to 0.4 mmol/L per decade. The decline in TC in most Western countries was the net effect of an increase in HDL cholesterol and a decline in non-HDL cholesterol, with the HDL cholesterol increase largest in New Zealand and Switzerland. Mean total-to-HDL cholesterol ratio declined in Japan, South Korea and most Western countries, by as much as similar to 0.7 per decade in Swiss men (equivalent to similar to 26% decline in coronary heart disease risk per decade). The ratio increased in China.Conclusions: HDL cholesterol has risen and the total-to-HDL cholesterol ratio has declined in many Western countries, Japan and South Korea, with only a weak correlation with changes in TC or non-HDL cholesterol.
AU  - NCD Risk Factors Collaboration (Müller-Nurasyid, M.
AU  - Döring, A.
AU  - Meisinger, C.
AU  - Peters, A.
AU  - Stöckl, D.)
C1  - 57407
C2  - 47746
CY  - Great Clarendon St, Oxford Ox2 6dp, England
SP  - 173-192
TI  - National trends in total cholesterol obscure heterogeneous changes in HDL and non-HDL cholesterol and total-to-HDL cholesterol ratio: A pooled analysis of 458 population-based studies in Asian and Western countries.
JO  - Int. J. Epidemiol.
VL  - 49
IS  - 1
PB  - Oxford Univ Press
PY  - 2020
SN  - 0300-5771
ER  - 

TY  - JOUR
AU  - Sebert, S.*
AU  - Lowry, E.*
AU  - Aumüller, N.*
AU  - Bermúdez, M.G.*
AU  - Bjerregaard, L.G.*
AU  - de Rooij, S.R.*
AU  - De Silva, M.*
AU  - El Marroun, H.*
AU  - Hummel, N.
AU  - Juola, T.*
AU  - Mason, G.*
AU  - Much, D.
AU  - Oliveros, E.*
AU  - Poupakis, S.*
AU  - Rautio, N.*
AU  - Schwarzfischer, P.*
AU  - Tzala, E.*
AU  - Uhl, O.*
AU  - van de Beek, C.*
AU  - Vehmeijer, F.*
AU  - Verdejo-Román, J.*
AU  - Wasenius, N.*
AU  - Webster, C.*
AU  - Ala-Mursula, L.*
AU  - Herzig, K.H.*
AU  - Keinänen-Kiukaanniemi, S.*
AU  - Miettunen, J.*
AU  - Baker, J.L.*
AU  - Campoy, C.*
AU  - Conti, G.*
AU  - Eriksson, J.G.*
AU  - Hummel, S.
AU  - Jaddoe, V.*
AU  - Koletzko, B.*
AU  - Lewin, A.*
AU  - Rodriguez-Palermo, M.*
AU  - Roseboom, T.*
AU  - Rueda, R.*
AU  - Evans, J.*
AU  - Felix, J.F.*
AU  - Prokopenko, I.*
AU  - Sørensen, T.I.A.*
AU  - Järvelin, M.R.*
C1  - 56598
C2  - 47169
CY  - Great Clarendon St, Oxford Ox2 6dp, England
SP  - 1051-1051K
TI  - Cohort Profile: The DynaHEALTH consortium - a European consortium for a life-course bio-psychosocial model of healthy ageing of glucose homeostasis.
JO  - Int. J. Epidemiol.
VL  - 48
IS  - 4
PB  - Oxford Univ Press
PY  - 2019
SN  - 0300-5771
ER  - 

TY  - JOUR
AU  - Felix, J.F.*
AU  - Joubert, B.R.*
AU  - Baccarelli, A.A.*
AU  - Sharp, G.C.*
AU  - Almqvist, C.*
AU  - Annesi-Maesano, I.*
AU  - Arshad, H.*
AU  - Baïz, N.*
AU  - Bakermans-Kranenburg, M.J.*
AU  - Bakulski, K.M.*
AU  - Binder, E.B.*
AU  - Bouchard, L.*
AU  - Breton, C.V.*
AU  - Brunekreef, B.*
AU  - Brunst, K.J.*
AU  - Burchard, E.G.*
AU  - Bustamante, M.*
AU  - Chatzi, L.*
AU  - Cheng Munthe-Kaas, M.*
AU  - Corpeleijn, E.*
AU  - Czamara, D.*
AU  - Dabelea, D.*
AU  - Davey Smith, G.*
AU  - De Boever, P.*
AU  - Duijts, L.*
AU  - Dwyer, T.*
AU  - Eng, C.*
AU  - Eskenazi, B.*
AU  - Everson, T.M.*
AU  - Falahi, F.*
AU  - Fallin, M.D.*
AU  - Farchi, S.*
AU  - Fernández, M.F.*
AU  - Gao, L.*
AU  - Gaunt, T.R.*
AU  - Ghantous, A.*
AU  - Gillman, M.W.*
AU  - Gonseth, S.*
AU  - Grote, V.*
AU  - Gruzieva, O.*
AU  - Håberg, S.E.*
AU  - Herceg, Z.*
AU  - Hivert, M.F.*
AU  - Holland, N.*
AU  - Holloway, J.W.*
AU  - Hoyo, C.*
AU  - Hu, D.*
AU  - Huang, R.C.*
AU  - Huen, K.*
AU  - Järvelin, M.R.*
AU  - Jima, D.D.*
AU  - Just, A.C.*
AU  - Karagas, M.R.*
AU  - Karlsson, R.*
AU  - Karmaus, W.*
AU  - Kechris, K.J.*
AU  - Kere, J.*
AU  - Kogevinas, M.*
AU  - Koletzko, B.*
AU  - Koppelman, G.H.*
AU  - Küpers, L.K.*
AU  - Ladd-Acosta, C.*
AU  - Lahti, J.*
AU  - Lambrechts, N.*
AU  - Langie, S.A.S.*
AU  - Lie, R.T.*
AU  - Liu, A.H.*
AU  - Magnus, M.C.*
AU  - Magnus, P.*
AU  - Maguire, R.L.*
AU  - Marsit, C.J.*
AU  - McArdle, W.*
AU  - Melén, E.*
AU  - Melton, P.*
AU  - Murphy, S.K.*
AU  - Nawrot, T.S.*
AU  - Nisticò, L.*
AU  - Nohr, E.A.*
AU  - Nordlund, B.*
AU  - Nystad, W.*
AU  - Oh, S.S.*
AU  - Oken, E.*
AU  - Page, C.M.*
AU  - Perron, P.*
AU  - Pershagen, G.*
AU  - Pizzi, C.*
AU  - Plusquin, M.*
AU  - Räikkönen, K.*
AU  - Reese, S.E.*
AU  - Reischl, E.
AU  - Richiardi, L.*
AU  - Ring, S.*
AU  - Roy, R.P.*
AU  - Rzehak, P.*
AU  - Schoeters, G.*
AU  - Schwartz, D.A.*
AU  - Sebert, S.*
AU  - Snieder, H.*
AU  - Sørensen, T.I.A.*
AU  - Starling, A.P.*
AU  - Sunyer, J.*
AU  - Taylor, J.A.*
AU  - Tiemeier, H.*
AU  - Ullemar, V.*
AU  - Vafeiadi, M.*
AU  - van IJzendoorn, M.H.*
AU  - Vonk, J.M.*
AU  - Vriens, A.*
AU  - Vrijheid, M.*
AU  - Wang, P.*
AU  - Wiemels, J.L.*
AU  - Wilcox, A.J.*
AU  - Wright, R.J.*
AU  - Xu, C.J.*
AU  - Xu, Z.*
AU  - Yang, I.V.*
AU  - Yousefi, P.*
AU  - Zhang, H.*
AU  - Zhang, W.*
AU  - Zhao, S.*
AU  - Agha, G.*
AU  - Relton, C.L.*
AU  - Jaddoe, V.W.V.*
AU  - London, S.J.*
C1  - 52092
C2  - 43722
CY  - Oxford
SP  - 22-23u
TI  - Cohort profile: Pregnancy and childhood epigenetics (PACE) consortium.
JO  - Int. J. Epidemiol.
VL  - 47
IS  - 1
PB  - Oxford Univ Press
PY  - 2018
SN  - 0300-5771
ER  - 

TY  - JOUR
AB  - Background: Metabolite networks are suggested to reflect biological pathways in health and disease. However, it is unknown whether such metabolite networks are reproducible across different populations. Therefore, the current study aimed to investigate similarity of metabolite networks in four German population-based studies. Methods: One hundred serum metabolites were quantified in European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam (n = 2458), EPIC-Heidelberg (n = 812), KORA (Cooperative Health Research in the Augsburg Region) (n = 3029) and CARLA (Cardiovascular Disease, Living and Ageing in Halle) (n = 1427) with targeted metabolomics. In a cross-sectional analysis, Gaussian graphical models were used to construct similar networks of 100 edges each, based on partial correlations of these metabolites. The four metabolite networks of the top 100 edges were compared based on (i) common features, i.e. number of common edges, Pearson correlation (r) and hamming distance (h); and (ii) meta-analysis of the four networks. Results: Among the four networks, 57 common edges and 66 common nodes (metabolites) were identified. Pairwise network comparisons showed moderate to high similarity (r = 63-0.96, h = 7-72), among the networks. Meta-analysis of the networks showed that, among the 100 edges and 89 nodes of the meta-analytic network, 57 edges and 66 metabolites were present in all the four networks, 58-76 edges and 75-89 nodes were present in at least three networks, and 63-84 edges and 76-87 edges were present in at least two networks. The meta-analytic network showed clear grouping of 10 sphingolipids, 8 lyso-phosphatidylcholines, 31 acyl-alkyl-phosphatidylcholines, 30 diacyl-phosphatidylcholines, 8 amino acids and 2 acylcarnitines. Conclusions: We found structural similarity in metabolite networks from four large studies. Using a meta-analytic network, as a new approach for combining metabolite data from different studies, closely related metabolites could be identified, for some of which the biological relationships in metabolic pathways have been previously described. They are candidates for further investigation to explore their potential role in biological processes.
AU  - Iqbal, K.*
AU  - Dietrich, S.*
AU  - Wittenbecher, C.*
AU  - Krumsiek, J.
AU  - Kühn, T.*
AU  - Lacruz, M.E.*
AU  - Kluttig, A.*
AU  - Prehn, C.
AU  - Adamski, J.
AU  - von Bergen, M.*
AU  - Kaaks, R.*
AU  - Schulze, M.B.*
AU  - Boeing, H.*
AU  - Floegel, A.*
C1  - 53745
C2  - 44991
SP  - 2070-2081
TI  - Comparison of metabolite networks from four German population-based studies.
JO  - Int. J. Epidemiol.
VL  - 47
IS  - 6
PY  - 2018
SN  - 0300-5771
ER  - 

TY  - JOUR
AB  - Background: Evidence from observational studies of telomere length (TL) has been conflicting regarding its direction of association with cancer risk. We investigated the causal relevance of TL for lung and head and neck cancers using Mendelian Randomization (MR) and mediation analyses.Methods: We developed a novel genetic instrument for TL in chromosome 5p15.33, using variants identified through deep-sequencing, that were genotyped in 2051 cancer-free subjects. Next, we conducted an MR analysis of lung (16 396 cases, 13 013 controls) and head and neck cancer (4415 cases, 5013 controls) using eight genetic instruments for TL. Lastly, the 5p15.33 instrument and distinct 5p15.33 lung cancer risk loci were evaluated using two-sample mediation analysis, to quantify their direct and indirect, telomere-mediated, effects.Results: The multi-allelic 5p15.33 instrument explained 1.49-2.00% of TL variation in our data (p = 2.6 x 10(-9)). The MR analysis estimated that a 1000 base-pair increase in TL increases risk of lung cancer [odds ratio (OR) = 1.41, 95% confidence interval (CI): 1.20-1.65] and lung adenocarcinoma (OR = 1.92, 95% CI: 1.51-2.22), but not squamous lung carcinoma (OR = 1.04, 95% CI: 0.83-1.29) or head and neck cancers (OR = 0.90, 95% CI: 0.70-1.05). Mediation analysis of the 5p15.33 instrument indicated an absence of direct effects on lung cancer risk (OR = 1.00, 95% CI: 0.95-1.04). Analysis of distinct 5p15.33 susceptibility variants estimated that TL mediates up to 40% of the observed associations with lung cancer risk.Conclusions: Our findings support a causal role for long telomeres in lung cancer aetiology, particularly for adenocarcinoma, and demonstrate that telomere maintenance partially mediates the lung cancer susceptibility conferred by 5p15.33 loci.
AU  - Kachuri, L.*
AU  - Saarela, O.*
AU  - Bojesen, S.E.*
AU  - Davey Smith, G.*
AU  - Liu, G.*
AU  - Landi, M.T.*
AU  - Caporaso, N.E.*
AU  - Christiani, D.C.*
AU  - Johansson, M.*
AU  - Panico, S.*
AU  - Overvad, K.*
AU  - Trichopoulou, A.*
AU  - Vineis, P.*
AU  - Scelo, G.*
AU  - Zaridze, D.*
AU  - Wu, X.*
AU  - Albanes, D.*
AU  - Diergaarde, B.*
AU  - Lagiou, P.*
AU  - Macfarlane, G.J.*
AU  - Aldrich, M.C.*
AU  - Tardón, A.*
AU  - Rennert, G.*
AU  - Olshan, A.F.*
AU  - Weissler, M.C.*
AU  - Chen, C.*
AU  - Goodman, G.E.*
AU  - Doherty, J.A.*
AU  - Ness, A.R.*
AU  - Bickeböller, H.*
AU  - Wichmann, H.-E.
AU  - Risch, A.*
AU  - Field, J.K.*
AU  - Teare, M.D.*
AU  - Kiemeney, L.A.*
AU  - van der Heijden, E.H.F.M.*
AU  - Carroll, J.C.*
AU  - Haugen, A.*
AU  - Zienolddiny, S.*
AU  - Skaug, V.*
AU  - Wünsch-Filho, V.*
AU  - Tajara, E.H.*
AU  - Ayoub Moysés, R.*
AU  - Daumas Nunes, F.*
AU  - Lam, S.*
AU  - Eluf-Neto, J.*
AU  - Lacko, M.*
AU  - Peters, W.H.M.*
AU  - Le Marchand, L.*
AU  - Duell, E.J.*
AU  - Andrew, A.S.*
AU  - Franceschi, S.*
AU  - Schabath, M.B.*
AU  - Manjer, J.*
AU  - Arnold, S.J.*
AU  - Lazarus, P.*
AU  - Mukeriya, A.*
AU  - Swiatkowska, B.*
AU  - Janout, V.*
AU  - Holcatova, I.*
AU  - Stojsic, J.*
AU  - Mates, D.*
AU  - Lissowska, J.*
AU  - Boccia, S.*
AU  - Lesseur, C.*
AU  - Zong, X.*
AU  - McKay, J.D.*
AU  - Brennan, P.*
AU  - Amos, C.I.*
AU  - Hung, R.J.*
C1  - 54652
C2  - 45737
CY  - Great Clarendon St, Oxford Ox2 6dp, England
SP  - 751-766
TI  - Mendelian Randomization and mediation analysis of leukocyte telomere length and risk of lung and head and neck cancers.
JO  - Int. J. Epidemiol.
VL  - 48
IS  - 3
PB  - Oxford Univ Press
PY  - 2018
SN  - 0300-5771
ER  - 

TY  - JOUR
AB  - Background: Change in the prevalence of raised blood pressure could be due to both shifts in the entire distribution of blood pressure (representing the combined effects of public health interventions and secular trends) and changes in its high-blood-pressure tail (representing successful clinical interventions to control blood pressure in the hypertensive population). Our aim was to quantify the contributions of these two phenomena to the worldwide trends in the prevalence of raised blood pressure.Methods: We pooled 1018 population-based studies with blood pressure measurements on 88.6 million participants from 1985 to 2016. We first calculated mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP) and prevalence of raised blood pressure by sex and 10-year age group from 20-29 years to 70-79 years in each study, taking into account complex survey design and survey sample weights, where relevant. We used a linear mixed effect model to quantify the association between (probit-transformed) prevalence of raised blood pressure and age-group-and sex-specific mean blood pressure. We calculated the contributions of change in mean SBP and DBP, and of change in the prevalence-mean association, to the change in prevalence of raised blood pressure.Results: In 2005-16, at the same level of population mean SBP and DBP, men and women in South Asia and in Central Asia, the Middle East and North Africa would have the highest prevalence of raised blood pressure, and men and women in the high-income Asia Pacific and high-income Western regions would have the lowest. In most region-sex-age groups where the prevalence of raised blood pressure declined, one half or more of the decline was due to the decline in mean blood pressure. Where prevalence of raised blood pressure has increased, the change was entirely driven by increasing mean blood pressure, offset partly by the change in the prevalence-mean association.Conclusions: Change in mean blood pressure is the main driver of the worldwide change in the prevalence of raised blood pressure, but change in the high-blood-pressure tail of the distribution has also contributed to the change in prevalence, especially in older age groups.
AU  - Zhou, B.*
AU  - Bentham, J.*
AU  - di Cesare, M.*
AU  - Bixby, H.*
AU  - Danaei, G.*
AU  - Hajifathalian, K.*
AU  - Taddei, C.*
AU  - Carrillo-Larco, R.M.*
AU  - Djalalinia, S.*
AU  - Khatibzadeh, S.*
AU  - Lugero, C.*
AU  - Peykari, N.*
AU  - Zhang, W.Z.*
AU  - Bennett, J.*
AU  - Bilano, V.*
AU  - Stevens, G.A.*
AU  - Cowan, M.J.*
AU  - Riley, L.M.*
AU  - Chen, Z.*
AU  - Hambleton, I.R.*
AU  - Jackson, R.T.*
AU  - Kengne, A.P.*
AU  - Khang, Y.*
AU  - Laxmaiah, A.*
AU  - Liu, J.*
AU  - Malekzadeh, R.*
AU  - Neuhauser, H.K.*
AU  - Soric, M.*
AU  - Starc, G.*
AU  - Sundström, J.*
AU  - Woodward, M.*
AU  - Ezzati, M.*
AU  - Abarca-Gomez, L.*
AU  - Abdeen, Z.A.*
AU  - Abu-Rmeileh, N.M.*
AU  - Acosta-Cazares, B.*
AU  - Ajlouni, K.*
AU  - Akhtaeva, N.*
AU  - Al-Raddadi, R.*
AU  - Ali, M.M.*
AU  - Ali, O.*
AU  - Aris, T.*
AU  - Arlappa, N.*
AU  - Arveiler, D.*
AU  - Aryal, K.K.*
AU  - Aspelund, T.*
AU  - Assah, F.K.*
AU  - Assuncao, M.C.F.*
AU  - Avdicova, M.*
AU  - NCD Risk Factors Collaboration (Döring, A.
AU  - Meisinger, C.
AU  - Müller-Nurasyid, M.
AU  - Peters, A.
AU  - Stieber, J.)
C1  - 54065
C2  - 45285
CY  - Great Clarendon St, Oxford Ox2 6dp, England
SP  - 872–883i
TI  - Contributions of mean and shape of blood pressure distribution to worldwide trends and variations in raised blood pressure: A pooled analysis of 1018 population-based measurement studies with 88.6 million participants.
JO  - Int. J. Epidemiol.
VL  - 47
IS  - 3
PB  - Oxford Univ Press
PY  - 2018
SN  - 0300-5771
ER  - 

TY  - JOUR
AB  - Background: Smoking is the strongest environmental risk factor for reduced pulmonary function. The genetic component of various pulmonary traits has also been demonstrated, and at least 26 loci have been reproducibly associated with either FEV1 (forced expiratory volume in 1 second) or FEV1/FVC (FEV1/forced vital capacity). Although the main effects of smoking and genetic loci are well established, the question of potential gene-by-smoking interaction effect remains unanswered. The aim of the present study was to assess, using a genetic risk score approach, whether the effect of these 26 loci on pulmonary function is influenced by smoking. Methods: We evaluated the interaction between smoking exposure, considered as either ever vs never or pack-years, and a 26-single nucleotide polymorphisms (SNPs) genetic risk score in relation to FEV1 or FEV1/FVC in 50 047 participants of European ancestry from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) and SpiroMeta consortia. Results: We identified an interaction (beta(int) = -0.036, 95% confidence interval, -0.040 to -0.032, P = 0.00057) between an unweighted 26 SNP genetic risk score and smoking status (ever/never) on the FEV1/FVC ratio. In interpreting this interaction, we showed that the genetic risk of falling below the FEV1/FVC threshold used to diagnose chronic obstructive pulmonary disease is higher among ever smokers than among never smokers. A replication analysis in two independent datasets, although not statistically significant, showed a similar trend in the interaction effect. Conclusions: This study highlights the benefit of using genetic risk scores for identifying interactions missed when studying individual SNPs and shows, for the first time, that persons with the highest genetic risk for low FEV1/FVC may be more susceptible to the deleterious effects of smoking.
AU  - Aschard, H.*
AU  - Tobin, M.D.*
AU  - Hancock, D.B.*
AU  - Skurnik, D.*
AU  - Sood, A.*
AU  - James, A.*
AU  - Smith, A.V.*
AU  - Manichaikul, A.*
AU  - Campbell, A.*
AU  - Prins, B.P.*
AU  - Hayward, C.*
AU  - Loth, D.W.*
AU  - Porteous, D.J.*
AU  - Strachan, D.P.*
AU  - Zeggini, E.*
AU  - O'Connor, G.T.*
AU  - Brusselle, G.G.*
AU  - Boezen, H.M.*
AU  - Schulz, H.
AU  - Deary, I.J.*
AU  - Hall, I.P.*
AU  - Rudan, I.*
AU  - Kaprio, J.*
AU  - Wilson, J.F.*
AU  - Wilk, J.B.*
AU  - Huffman, J.E.*
AU  - Zhao, J.H.*
AU  - de Jong, K.*
AU  - Lyytikäinen, L.-P.*
AU  - Wain, L.V.*
AU  - Jarvelin, M.R.*
AU  - Kähönen, M.*
AU  - Fornage, M.*
AU  - Polasek, O.*
AU  - Cassano, P.A.*
AU  - Barr, R.G.*
AU  - Rawal, R.
AU  - Harris, S.E.*
AU  - Gharib, S.A.*
AU  - Enroth, S.*
AU  - Heckbert, S.R.*
AU  - Lehtimäki, T.*
AU  - Gyllensten, U.*
AU  - Jackson, V.E.*
AU  - Gudnason, V.*
AU  - Tang, W.*
AU  - Dupuis, J.*
AU  - Artigas, M.S.*
AU  - Joshi, A.D.*
AU  - London, S.J.*
AU  - Kraft, P.*
C1  - 51697
C2  - 43374
CY  - Oxford
SP  - 894-904
TI  - Evidence for large-scale gene-by-smoking interaction effects on pulmonary function.
JO  - Int. J. Epidemiol.
VL  - 46
IS  - 3
PB  - Oxford Univ Press
PY  - 2017
SN  - 0300-5771
ER  - 

TY  - JOUR
AB  - BACKGROUND: Whereas it is generally accepted that maternal environment plays a key role in child health, emerging evidence suggests that paternal environment before conception also impacts child health. We aimed to investigate the association between children's asthma risk and parental smoking and welding exposures prior to conception. METHODS: In a longitudinal, multi-country study, parents of 24 168 offspring aged 2-51 years provided information on their life-course smoking habits, occupational exposure to welding and metal fumes, and offspring's asthma before/after age 10 years and hay fever. Logistic regressions investigated the relevant associations controlled for age, study centre, parental characteristics (age, asthma, education) and clustering by family. RESULTS: Non-allergic early-onset asthma (asthma without hay fever, present in 5.8%) was more common in the offspring with fathers who smoked before conception {odds ratio [OR] = 1.68 [95% confidence interval (CI) = 1.18-2.41]}, whereas mothers' smoking before conception did not predict offspring asthma. The risk was highest if father started smoking before age 15 years [3.24 (1.67-6.27)], even if he stopped more than 5 years before conception [2.68 (1.17-6.13)]. Fathers' pre-conception welding was independently associated with non-allergic asthma in his offspring [1.80 (1.29-2.50)]. There was no effect if the father started welding or smoking after birth. The associations were consistent across countries. CONCLUSIONS: Environmental exposures in young men appear to influence the respiratory health of their offspring born many years later. Influences during susceptible stages of spermatocyte development might be important and needs further investigation in humans. We hypothesize that protecting young men from harmful exposures may lead to improved respiratory health in future generations.
AU  - Svanes, C.*
AU  - Koplin, J.*
AU  - Skulstad, S.M.*
AU  - Johannessen, A.*
AU  - Bertelsen, R.J.*
AU  - Benediktsdottir, B.*
AU  - Bråbäck, L.*
AU  - Elie Carsin, A.*
AU  - Dharmage, S.*
AU  - Dratva, J.*
AU  - Forsberg, B.*
AU  - Gislason, T.*
AU  - Heinrich, J.
AU  - Holm, M.*
AU  - Janson, C.*
AU  - Jarvis, D.*
AU  - Jõgi, R.*
AU  - Krauss-Etschmann, S.*
AU  - Lindberg, E.*
AU  - Macsali, F.*
AU  - Malinovschi, A.*
AU  - Modig, L.*
AU  - Norbäck, D.*
AU  - Omenaas, E.*
AU  - Waatevik Saure, E.*
AU  - Sigsgaard, T.*
AU  - Skorge, T.D.*
AU  - Svanes, O.*
AU  - Torén, K.*
AU  - Torres, C.*
AU  - Schlünssen, V.*
AU  - Gómez Real, F.*
C1  - 49334
C2  - 41751
CY  - Oxford
SP  - 235-245
TI  - Father's environment before conception and asthma risk in his children: A multi-generation analysis of the respiratory health In Northern Europe study.
JO  - Int. J. Epidemiol.
VL  - 46
IS  - 1
PB  - Oxford Univ Press
PY  - 2017
SN  - 0300-5771
ER  - 

TY  - JOUR
AB  - BACKGROUND: The application of metabolomics in prospective cohort studies is statistically challenging. Given the importance of appropriate statistical methods for selection of disease-associated metabolites in highly correlated complex data, we combined random survival forest (RSF) with an automated backward elimination procedure that addresses such issues. METHODS: Our RSF approach was illustrated with data from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study, with concentrations of 127 serum metabolites as exposure variables and time to development of type 2 diabetes mellitus (T2D) as outcome variable. Out of this data set, Cox regression with a stepwise selection method was recently published. Replication of methodical comparison (RSF and Cox regression) was conducted in two independent cohorts. Finally, the R-code for implementing the metabolite selection procedure into the RSF-syntax is provided. RESULTS: The application of the RSF approach in EPIC-Potsdam resulted in the identification of 16 incident T2D-associated metabolites which slightly improved prediction of T2D when used in addition to traditional T2D risk factors and also when used together with classical biomarkers. The identified metabolites partly agreed with previous findings using Cox regression, though RSF selected a higher number of highly correlated metabolites. CONCLUSIONS: The RSF method appeared to be a promising approach for identification of disease-associated variables in complex data with time to event as outcome. The demonstrated RSF approach provides comparable findings as the generally used Cox regression, but also addresses the problem of multicollinearity and is suitable for high-dimensional data.
AU  - Dietrich, S.*
AU  - Floegel, A.*
AU  - Troll, M.
AU  - Kuhn, T.*
AU  - Rathmann, W.*
AU  - Peters, A.
AU  - Sookthai, D.*
AU  - von Bergen, M.*
AU  - Kaaks, R.*
AU  - Adamski, J.
AU  - Prehn, C.
AU  - Boeing, H.*
AU  - Schulze, M.B.*
AU  - Illig, T.*
AU  - Pischon, T.*
AU  - Knüppel, S.*
AU  - Wang-Sattler, R.
AU  - Drogan, D.*
C1  - 49363
C2  - 41774
CY  - Oxford
SP  - 1406-1420
TI  - Random survival forest in practice: A method for modelling complex metabolomics data in time to event analysis.
JO  - Int. J. Epidemiol.
VL  - 45
IS  - 1
PB  - Oxford Univ Press
PY  - 2016
SN  - 0300-5771
ER  - 

TY  - JOUR
AU  - Lowe, A.J.*
AU  - Lodge, C.J.*
AU  - Allen, K.J.*
AU  - Abramson, M.J.*
AU  - Matheson, M.C.*
AU  - Thomas, P.S.*
AU  - Barton, C.A.*
AU  - Bennett, C.M.*
AU  - Erbas, B.*
AU  - Svanes, C.*
AU  - Wjst, M.
AU  - Gómez Real, F.*
AU  - Perret, J.L.*
AU  - Russell, M.A.*
AU  - Southey, M.C.*
AU  - Hopper, J.L.*
AU  - Gurrin, L.C.*
AU  - Axelrad, C.J.*
AU  - Hill, D.J.*
AU  - Dharmage, S.C.*
C1  - 48609
C2  - 41215
CY  - Oxford
SP  - 25-26
TI  - Cohort profile: Melbourne Atopy Cohort study (MACS).
JO  - Int. J. Epidemiol.
VL  - 46
IS  - 1
PB  - Oxford Univ Press
PY  - 2016
SN  - 0300-5771
ER  - 

TY  - JOUR
AB  - BACKGROUND: Numerous observational studies have observed associations between vitamin D deficiency and cardiometabolic diseases, but these findings might be confounded by obesity. A characterization of the metabolic profile associated with serum 25-hydroxyvitamin D [25(OH)D] levels, in general and stratified by abdominal obesity, may help to untangle the relationship between vitamin D, obesity and cardiometabolic health. METHODS: Serum metabolomics measurements were obtained from a nuclear magnetic resonance spectroscopy (NMR)- and a mass spectrometry (MS)-based platform. The discovery was conducted in 1726 participants of the population-based KORA-F4 study, in which the associations of the concentrations of 415 metabolites with 25(OH)D levels were assessed in linear models. The results were replicated in 6759 participants (NMR) and 609 (MS) participants, respectively, of the population-based FINRISK 1997 study. RESULTS: Mean [standard deviation (SD)] 25(OH)D levels were 15.2 (7.5) ng/ml in KORA F4 and 13.8 (5.9) ng/ml in FINRISK 1997; 37 metabolites were associated with 25(OH)D in KORA F4 at P < 0.05/415. Of these, 30 associations were replicated in FINRISK 1997 at P < 0.05/37. Among these were constituents of (very) large very-low-density lipoprotein and small low-density lipoprotein subclasses and related measures like serum triglycerides as well as fatty acids and measures reflecting the degree of fatty acid saturation. The observed associations were independent of waist circumference and generally similar in abdominally obese and non-obese participants. CONCLUSIONS: Independently of abdominal obesity, higher 25(OH)D levels were associated with a metabolite profile characterized by lower concentrations of atherogenic lipids and a higher degree of fatty acid polyunsaturation. These results indicate that the relationship between vitamin D deficiency and cardiometabolic diseases is unlikely to merely reflect obesity-related pathomechanisms.
AU  - Vogt, S.
AU  - Wahl, S.
AU  - Kettunen, J.*
AU  - Breitner-Busch, S.
AU  - Kastenmüller, G.
AU  - Gieger, C.
AU  - Suhre, K.
AU  - Waldenberger, M.
AU  - Kratzsch, J.*
AU  - Perola, M.*
AU  - Salomaa, V.*
AU  - Blankenberg, S.*
AU  - Zeller, T.*
AU  - Soininen, P.*
AU  - Kangas, A.J.*
AU  - Peters, A.
AU  - Grallert, H.
AU  - Ala-Korpela, M.*
AU  - Thorand, B.
C1  - 49453
C2  - 32123
CY  - Oxford
SP  - 1469-1481
TI  - Characterization of the metabolic profile associated with serum 25-hydroxyvitamin D: A cross-sectional analysis in population-based data.
JO  - Int. J. Epidemiol.
VL  - 45
IS  - 5
PB  - Oxford Univ Press
PY  - 2016
SN  - 0300-5771
ER  - 

TY  - JOUR
AB  - Background: Short-term exposure to air pollution is associated with morbidity and mortality. Metabolites are intermediaries in biochemical processes, and associations between air pollution and metabolites can yield unique mechanistic insights. Methods: We used independent cross-sectional samples with targeted metabolomics (138 metabolites across five metabolite classes) from three cohort studies, each a part of the Cooperative Health Research in the Region of Augsburg (KORA). The KORA cohorts are numbered (1 to 4) according to which survey they belong to, and lettered S or F according to whether the survey was a baseline or follow-up survey. KORA F4 (N = 3044) served as our discovery cohort, with KORA S4 (N = 485) serving as the primary replication cohort. KORA F4 and KORA S4 were primarily fasting cohorts. We used the non-fasting KORA F3 (N = 377) cohort to evaluate replicated associations in non-fasting individuals, and we performed a random effects meta-analysis of all three cohorts. Associations between the 0–4-day lags and the 5-day average of particulate matter (PM)2.5, NO2 and ozone were modelled via generalized additive models. All air pollution exposures were scaled to the interquartile range, and effect estimates presented as percent changes relative to the geometric mean of the metabolite concentration (ΔGM). Results: There were 10 discovery cohort associations, of which seven were lysophosphatidylcholines (LPCs); NO2 was the most ubiquitous exposure (5/10). The 5-day average NO2-LPC(28:0) association was associated at a Bonferroni corrected P-value threshold (P < 1.2x10−4) in KORA F4 [ΔGM = 11.5%; 95% confidence interval (CI) = 6.60, 16.3], and replicated (P < 0.05) in KORA S4 (ΔGM = 21.0%; CI = 4.56, 37.5). This association was not observed in the non-fasting KORA F3 cohort (ΔGM = −5.96%; CI = −26.3, 14.3), but remained in the random effects meta-analysis (ΔGM = 10.6%; CI = 0.16, 21). Conclusions: LPCs are associated with short-term exposure to air pollutants, in particular NO2. Further research is needed to understand the effect of nutritional/fasting status on these associations and the causal mechanisms linking air pollution exposure and metabolite profiles.
AU  - Ward-Caviness, C.K.
AU  - Breitner-Busch, S.
AU  - Wolf, K.
AU  - Cyrys, J.
AU  - Kastenmüller, G.
AU  - Wang-Sattler, R.
AU  - Schneider, A.E.
AU  - Peters, A.
C1  - 50109
C2  - 42024
CY  - Oxford
SP  - 1528-1538
TI  - Short-term NO2 exposure is associated with long-chain fatty acids in prospective cohorts from Augsburg, Germany: Results from an analysis of 138 metabolites and three exposures.
JO  - Int. J. Epidemiol.
VL  - 45
IS  - 5
PB  - Oxford Univ Press
PY  - 2016
SN  - 0300-5771
ER  - 

TY  - JOUR
AB  - BACKGROUND: Adiposity, as indicated by body mass index (BMI), has been associated with risk of cardiovascular diseases in epidemiological studies. We aimed to investigate if these associations are causal, using Mendelian randomization (MR) methods. METHODS: The associations of BMI with cardiovascular outcomes [coronary heart disease (CHD), heart failure and ischaemic stroke], and associations of a genetic score (32 BMI single nucleotide polymorphisms) with BMI and cardiovascular outcomes were examined in up to 22 193 individuals with 3062 incident cardiovascular events from nine prospective follow-up studies within the ENGAGE consortium. We used random-effects meta-analysis in an MR framework to provide causal estimates of the effect of adiposity on cardiovascular outcomes. RESULTS: There was a strong association between BMI and incident CHD (HR = 1.20 per SD-increase of BMI, 95% CI, 1.12-1.28, P = 1.9·10(-7)), heart failure (HR = 1.47, 95% CI, 1.35-1.60, P = 9·10(-19)) and ischaemic stroke (HR = 1.15, 95% CI, 1.06-1.24, P = 0.0008) in observational analyses. The genetic score was robustly associated with BMI (β = 0.030 SD-increase of BMI per additional allele, 95% CI, 0.028-0.033, P = 3·10(-107)). Analyses indicated a causal effect of adiposity on development of heart failure (HR = 1.93 per SD-increase of BMI, 95% CI, 1.12-3.30, P = 0.017) and ischaemic stroke (HR = 1.83, 95% CI, 1.05-3.20, P = 0.034). Additional cross-sectional analyses using both ENGAGE and CARDIoGRAMplusC4D data showed a causal effect of adiposity on CHD. CONCLUSIONS: Using MR methods, we provide support for the hypothesis that adiposity causes CHD, heart failure and, previously not demonstrated, ischaemic stroke.
AU  - Hägg, S.*
AU  - Fall, T.*
AU  - Ploner, A.*
AU  - Mägi, R.*
AU  - Fischer, K.*
AU  - Draisma, H.H.*
AU  - Kals, M.*
AU  - de Vries, P.S.*
AU  - Dehghan, A.
AU  - Willems, S.M.
AU  - Sarin, A.P.*
AU  - Kristiansson, K.*
AU  - Nuotio, M.L.*
AU  - Havulinna, A.S.*
AU  - de Bruijn, R.F.*
AU  - Ikram, M.A.*
AU  - Kuningas, M.*
AU  - Stricker, B.H.*
AU  - Franco, O.H.*
AU  - Benyamin, B.*
AU  - Gieger, C.
AU  - Hall, A.S.*
AU  - Huikari, V.*
AU  - Jula, A.*
AU  - Jarvelin, M.R.*
AU  - Kaakinen, M.*
AU  - Kaprio, J.*
AU  - Kobl, M.
AU  - Mangino, M.*
AU  - Nelson, C.P.*
AU  - Palotie, A.*
AU  - Samani, N.J.*
AU  - Spector, T.D.*
AU  - Strachan, D.P.*
AU  - Tobin, M.D.*
AU  - Whitfield, J.B.*
AU  - Uitterlinden, A.G.*
AU  - Salomaa, V.*
AU  - Syvanen, A.C.*
AU  - Kuulasmaa, K.*
AU  - Magnusson, P.K.*
AU  - Esko, T.*
AU  - Hofman, A.*
AU  - de Geus, E.J.*
AU  - Lind, L.*
AU  - Giedraitis, V.*
AU  - Perola, M.*
AU  - Evans, A.*
AU  - Ferrieres, J.*
AU  - Virtamo, J.*
AU  - Kee, F.*
AU  - Tregouet, D.A.*
AU  - Arveiler, D.*
AU  - Amouyel, P.*
AU  - Gianfagna, F.*
AU  - Brambilla, P.*
AU  - Ripatti, S.*
AU  - van Duijn, C.M.*
AU  - Metspalu, A.*
AU  - Prokopenko, I.*
AU  - McCarthy, M.I.*
AU  - Pedersen, N.L.*
AU  - Ingelsson, E.*
AU  - ENGAGE Consortium (Döring, A.
AU  - Nitz, B.
AU  - Rawal, R.
AU  - Wichmann, H.-E.)
C1  - 45052
C2  - 37191
CY  - Oxford
SP  - 578-586
TI  - Adiposity as a cause of cardiovascular disease: A Mendelian randomization study.
JO  - Int. J. Epidemiol.
VL  - 44
IS  - 2
PB  - Oxford Univ Press
PY  - 2015
SN  - 0300-5771
ER  - 

TY  - JOUR
AB  - Background: For men and women, taller height is associated with increased risk of all cancers combined. For colorectal cancer (CRC), it is unclear whether the differential association of height by sex is real or is due to confounding or bias inherent in observational studies. We performed a Mendelian randomization study to examine the association between height and CRC risk. Methods: To minimize confounding and bias, we derived a weighted genetic risk score predicting height (using 696 genetic variants associated with height) in 10 226 CRC cases and 10 286 controls. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for associations between height, genetically predicted height and CRC. Results: Using conventional methods, increased height (per 10-cm increment) was associated with increased CRC risk (OR = 1.08, 95% CI = 1.02-1.15). In sex-specific analyses, height was associated with CRC risk for women (OR = 1.15, 95% CI = 1.05-1.26), but not men (OR = 0.98, 95% CI = 0.92-1.05). Consistent with these results, carrying greater numbers of (weighted) height-increasing alleles (per 1-unit increase) was associated with higher CRC risk for women and men combined (OR = 1.07, 95% CI = 1.01-1.14) and for women (OR = 1.09, 95% CI = 1.01-1.19). There was weaker evidence of an association for men (OR = 1.05, 95% CI = 0.96-1.15). Conclusion: We provide evidence for a causal association between height and CRC for women. The CRC-height association for men remains unclear and warrants further investigation in other large studies.
AU  - Thrift, A.P.*
AU  - Gong, J.*
AU  - Peters, U.*
AU  - Chang-Claude, J.*
AU  - Rudolph, A.*
AU  - Slattery, M.L.*
AU  - Chan, A.T.*
AU  - Esko, T.*
AU  - Wood, A.R.*
AU  - Yang, J.*
AU  - Vedantam, S.*
AU  - Gustafsson, S.*
AU  - Pers, T.H.*
AU  - GIANT Consortium (Albrecht, E.
AU  - Gieger, C.
AU  - Grallert, H.
AU  - Heid, I.M.
AU  - Illig, T.
AU  - Müller-Nurasyid, M.
AU  - Peters, A.
AU  - Thorand, B.
AU  - Wichmann, H.-E.)
AU  - Baron, J.A.*
AU  - Bézieau, S.*
AU  - Kuery, S.*
AU  - Ogino, S.*
AU  - Berndt, S.I.*
AU  - Casey, G.*
AU  - Haile, R.W.*
AU  - Du, M.*
AU  - Harrison, T.A.*
AU  - Thornquist, M.*
AU  - Duggan, D.J.*
AU  - Le Marchand, L.*
AU  - Lemire, M.
AU  - Lindor, N.M.*
AU  - Seminara, D.*
AU  - Song, M.*
AU  - Thibodeau, S.N.*
AU  - Cotterchio, M.*
AU  - Win, A.K.*
AU  - Jenkins, M.A.*
AU  - Hopper, J.L.*
AU  - Ulrich, C.M.*
AU  - Potter, J.D.*
AU  - Newcomb, P.A.*
AU  - Schoen, R.E.*
AU  - Hoffmeister, M.*
AU  - Brenner, H.*
AU  - White, E.S.*
AU  - Hsu, L.A.*
AU  - Campbell, P.T.*
C1  - 46405
C2  - 37755
CY  - Oxford
SP  - 662-672
TI  - Mendelian randomization study of height and risk of colorectal cancer.
JO  - Int. J. Epidemiol.
VL  - 44
IS  - 2
PB  - Oxford Univ Press
PY  - 2015
SN  - 0300-5771
ER  - 

TY  - JOUR
AB  - BACKGROUND: Research in modern biomedicine and social science requires sample sizes so large that they can often only be achieved through a pooled co-analysis of data from several studies. But the pooling of information from individuals in a central database that may be queried by researchers raises important ethico-legal questions and can be controversial. In the UK this has been highlighted by recent debate and controversy relating to the UK's proposed 'care.data' initiative, and these issues reflect important societal and professional concerns about privacy, confidentiality and intellectual property. DataSHIELD provides a novel technological solution that can circumvent some of the most basic challenges in facilitating the access of researchers and other healthcare professionals to individual-level data. METHODS: Commands are sent from a central analysis computer (AC) to several data computers (DCs) storing the data to be co-analysed. The data sets are analysed simultaneously but in parallel. The separate parallelized analyses are linked by non-disclosive summary statistics and commands transmitted back and forth between the DCs and the AC. This paper describes the technical implementation of DataSHIELD using a modified R statistical environment linked to an Opal database deployed behind the computer firewall of each DC. Analysis is controlled through a standard R environment at the AC. RESULTS: Based on this Opal/R implementation, DataSHIELD is currently used by the Healthy Obese Project and the Environmental Core Project (BioSHaRE-EU) for the federated analysis of 10 data sets across eight European countries, and this illustrates the opportunities and challenges presented by the DataSHIELD approach. CONCLUSIONS: DataSHIELD facilitates important research in settings where: (i) a co-analysis of individual-level data from several studies is scientifically necessary but governance restrictions prohibit the release or sharing of some of the required data, and/or render data access unacceptably slow; (ii) a research group (e.g. in a developing nation) is particularly vulnerable to loss of intellectual property-the researchers want to fully share the information held in their data with national and international collaborators, but do not wish to hand over the physical data themselves; and (iii) a data set is to be included in an individual-level co-analysis but the physical size of the data precludes direct transfer to a new site for analysis.
AU  - Gaye, A.*
AU  - Marcon, Y.*
AU  - Isaeva, J.*
AU  - LaFlamme, P.*
AU  - Turner, A.*
AU  - Jones, E.M.*
AU  - Minion, J.*
AU  - Boyd, A.W.*
AU  - Newby, C.J.*
AU  - Nuotio, M.L.*
AU  - Wilson, R.*
AU  - Butters, O.*
AU  - Murtagh, B.*
AU  - Demir, I.E.*
AU  - Doiron, D.*
AU  - Giepmans, L.*
AU  - Wallace, S.E.*
AU  - Budin-Ljøsne, I.*
AU  - Schmidt, C.O.*
AU  - Boffetta, P.*
AU  - Boniol, M.*
AU  - Bota, M.*
AU  - Carter, K.W.*
AU  - deKlerk, N.*
AU  - Dibben, C.*
AU  - Francis, R.W.*
AU  - Hiekkalinna, T.*
AU  - Hveem, K.*
AU  - Kvaløy, K.*
AU  - Millar, S.*
AU  - Perry, I.J.*
AU  - Peters, A.
AU  - Phillips, C.M.*
AU  - Popham, F.*
AU  - Raab, G.*
AU  - Reischl, E.
AU  - Sheehan, N.*
AU  - Waldenberger, M.
AU  - Perola, M.*
AU  - van den Heuvel, E.*
AU  - Macleod, J.*
AU  - Knoppers, B.M.*
AU  - Stolk, R.P.*
AU  - Fortier, I.*
AU  - Harris, J.R.*
AU  - Woffenbuttel, B.H.*
AU  - Murtagh, M.J.*
AU  - Ferretti, V.*
AU  - Burton, P.R*
C1  - 43258
C2  - 36274
SP  - 1929-1944
TI  - DataSHIELD: Taking the analysis to the data, not the data to the analysis.
JO  - Int. J. Epidemiol.
VL  - 43
IS  - 6
PY  - 2014
SN  - 0300-5771
ER  - 

TY  - JOUR
AB  - BACKGROUND: Human ageing is a complex, multifactorial process and early developmental factors affect health outcomes in old age. METHODS: Metabolomic profiling on fasting blood was carried out in 6055 individuals from the UK. Stepwise regression was performed to identify a panel of independent metabolites which could be used as a surrogate for age. We also investigated the association with birthweight overall and within identical discordant twins and with genome-wide methylation levels. RESULTS: We identified a panel of 22 metabolites which combined are strongly correlated with age (R(2) = 59%) and with age-related clinical traits independently of age. One particular metabolite, C-glycosyl tryptophan (C-glyTrp), correlated strongly with age (beta = 0.03, SE = 0.001, P = 7.0 × 10(-157)) and lung function (FEV1 beta = -0.04, SE = 0.008, P = 1.8 × 10(-8) adjusted for age and confounders) and was replicated in an independent population (n = 887). C-glyTrp was also associated with bone mineral density (beta = -0.01, SE = 0.002, P = 1.9 × 10(-6)) and birthweight (beta = -0.06, SE = 0.01, P = 2.5 × 10(-9)). The difference in C-glyTrp levels explained 9.4% of the variance in the difference in birthweight between monozygotic twins. An epigenome-wide association study in 172 individuals identified three CpG-sites, associated with levels of C-glyTrp (P < 2 × 10(-6)). We replicated one CpG site in the promoter of the WDR85 gene in an independent sample of 350 individuals (beta = -0.20, SE = 0.04, P = 2.9 × 10(-8)). WDR85 is a regulator of translation elongation factor 2, essential for protein synthesis in eukaryotes. CONCLUSIONS: Our data illustrate how metabolomic profiling linked with epigenetic studies can identify some key molecular mechanisms potentially determined in early development that produce long-term physiological changes influencing human health and ageing.
AU  - Menni, C.*
AU  - Kastenmüller, G.
AU  - Petersen, A.-K.
AU  - Bell, J.T.*
AU  - Psatha, M.*
AU  - Tsai, P.C.*
AU  - Gieger, C.
AU  - Schulz, H.
AU  - Erte, I.*
AU  - John, S.*
AU  - Brosnan, M.J.*
AU  - Wilson, S.G.*
AU  - Tsaprouni, L.*
AU  - Lim, E.M.*
AU  - Stuckey, B.*
AU  - Deloukas, P.*
AU  - Mohney, R.P.*
AU  - Suhre, K.
AU  - Spector, T.D.*
AU  - Valdes, A.M.*
C1  - 28147
C2  - 32963
SP  - 1111-1119
TI  - Metabolomic markers reveal novel pathways of ageing and early development in human populations.
JO  - Int. J. Epidemiol.
VL  - 42
IS  - 4
PB  - Oxford Univ. Press
PY  - 2013
SN  - 0300-5771
ER  - 

TY  - JOUR
AB  - BACKGROUND: The extent to which adult height, a biomarker of the interplay of genetic endowment and early-life experiences, is related to risk of chronic diseases in adulthood is uncertain. METHODS: We calculated hazard ratios (HRs) for height, assessed in increments of 6.5 cm, using individual-participant data on 174 374 deaths or major non-fatal vascular outcomes recorded among 1 085 949 people in 121 prospective studies. RESULTS: For people born between 1900 and 1960, mean adult height increased 0.5-1 cm with each successive decade of birth. After adjustment for age, sex, smoking and year of birth, HRs per 6.5 cm greater height were 0.97 (95% confidence interval: 0.96-0.99) for death from any cause, 0.94 (0.93-0.96) for death from vascular causes, 1.04 (1.03-1.06) for death from cancer and 0.92 (0.90-0.94) for death from other causes. Height was negatively associated with death from coronary disease, stroke subtypes, heart failure, stomach and oral cancers, chronic obstructive pulmonary disease, mental disorders, liver disease and external causes. In contrast, height was positively associated with death from ruptured aortic aneurysm, pulmonary embolism, melanoma and cancers of the pancreas, endocrine and nervous systems, ovary, breast, prostate, colorectum, blood and lung. HRs per 6.5 cm greater height ranged from 1.26 (1.12-1.42) for risk of melanoma death to 0.84 (0.80-0.89) for risk of death from chronic obstructive pulmonary disease. HRs were not appreciably altered after further adjustment for adiposity, blood pressure, lipids, inflammation biomarkers, diabetes mellitus, alcohol consumption or socio-economic indicators. CONCLUSION: Adult height has directionally opposing relationships with risk of death from several different major causes of chronic diseases.
AU  - Emerging Risk Factors Collaboration (Döring, A.
AU  - Meisinger, C.)
C1  - 10954
C2  - 30456
SP  - 1419-1433
TI  - Adult height and the risk of cause-specific death and vascular morbidity in 1 million people: Individual participant meta-analysis.
JO  - Int. J. Epidemiol.
VL  - 41
IS  - 5
PB  - Oxford Univ. Press
PY  - 2012
SN  - 0300-5771
ER  - 

TY  - JOUR
AB  - BACKGROUND: Genetic differences between men and women may contribute to sex differences in prevalence and progression of many common complex diseases. Using the WTCCC GWAS, we analysed whether there are sex-specific differences in effect size estimates at 142 established loci for seven complex diseases: rheumatoid arthritis, type 1 diabetes (T1D), Crohn's disease, type 2 diabetes (T2D), hypertension, coronary artery disease and bipolar disorder. METHODS: For each Single nucleotide polymorphism (SNP), we calculated the per-allele odds ratio for each sex and the relative odds ratios (RORs; the effect size is higher in men with ROR greater than one). RORs were then meta-analysed across loci within each disease and across diseases. RESULTS: For each disease, summary RORs were not different from one, but there was between-SNP heterogeneity in the RORs for T1D and T2D. Four loci in T1D, three in Crohn's disease and three in T2D showed differences in the genetic effect between men and women (P < 0.05). We probed these differences in additional independent replication samples for T1D and T2D. The differences remained for the T1D loci CTSH, 17q21 and 20p13 and the T2D locus BCL11A, when WTCCC data and replication data were meta-analysed. Only CTSH showed different genetic effect between men and women in the replication data alone. CONCLUSION: Our results exclude the presence of large and frequent differences in the effect size estimates between men and women for the established loci in the seven common diseases explored. Documenting small differences in genetic effects between men and women requires large studies and systematic evaluation.
AU  - Orozco, G.*
AU  - Ioannidis, J.P.*
AU  - Morris, A.*
AU  - Zeggini, E.*
AU  - DIAGRAM Consortium (Gieger, C.
AU  - Grallert, H.
AU  - Huth, C.
AU  - Illig, T.
AU  - Klopp, N.
AU  - Meitinger, T.
AU  - Petersen, A.-K.
AU  - Thorand, B.
AU  - Wichmann, H.-E.)
C1  - 11018
C2  - 30466
SP  - 1376-1382
TI  - Sex-specific differences in effect size estimates at established complex trait loci.
JO  - Int. J. Epidemiol.
VL  - 41
IS  - 5
PB  - Oxford Univ. Press
PY  - 2012
SN  - 0300-5771
ER  - 

TY  - JOUR
AB  - BACKGROUND: Proper understanding of the roles of, and interactions between genetic, lifestyle, environmental and psycho-social factors in determining the risk of development and/or progression of chronic diseases requires access to very large high-quality databases. Because of the financial, technical and time burdens related to developing and maintaining very large studies, the scientific community is increasingly synthesizing data from multiple studies to construct large databases. However, the data items collected by individual studies must be inferentially equivalent to be meaningfully synthesized. The DataSchema and Harmonization Platform for Epidemiological Research (DataSHaPER; http://www.datashaper.org) was developed to enable the rigorous assessment of the inferential equivalence, i.e. the potential for harmonization, of selected information from individual studies. METHODS: This article examines the value of using the DataSHaPER for retrospective harmonization of established studies. Using the DataSHaPER approach, the potential to generate 148 harmonized variables from the questionnaires and physical measures collected in 53 large population-based studies (6.9 million participants) was assessed. Variable and study characteristics that might influence the potential for data synthesis were also explored. RESULTS: Out of all assessment items evaluated (148 variables for each of the 53 studies), 38% could be harmonized. Certain characteristics of variables (i.e. relative importance, individual targeted, reference period) and of studies (i.e. observational units, data collection start date and mode of questionnaire administration) were associated with the potential for harmonization. For example, for variables deemed to be essential, 62% of assessment items paired could be harmonized. CONCLUSION: The current article shows that the DataSHaPER provides an effective and flexible approach for the retrospective harmonization of information across studies. To implement data synthesis, some additional scientific, ethico-legal and technical considerations must be addressed. The success of the DataSHaPER as a harmonization approach will depend on its continuing development and on the rigour and extent of its use. The DataSHaPER has the potential to take us closer to a truly collaborative epidemiology and offers the promise of enhanced research potential generated through synthesized databases.
AU  - Fortier, I.*
AU  - Doiron, D.*
AU  - Little, J.*
AU  - Ferretti, V.*
AU  - L'Heureux, F.*
AU  - Stolk, R.P.*
AU  - Knoppers, B.M.*
AU  - Hudson, T.J.*
AU  - Burton, P.R*
AU  - International Harmonization Initiative (Döring, A.
AU  - Wichmann, H.-E.)
C1  - 6810
C2  - 29294
SP  - 1314-1328
TI  - Is rigorous retrospective harmonization possible? Application of the DataSHaPER approach across 53 large studies.
JO  - Int. J. Epidemiol.
VL  - 40
IS  - 5
PB  - Oxford Univ. Press
PY  - 2011
SN  - 0300-5771
ER  - 

TY  - JOUR
AB  - BACKGROUND: Vast sample sizes are often essential in the quest to disentangle the complex interplay of the genetic, lifestyle, environmental and social factors that determine the aetiology and progression of chronic diseases. The pooling of information between studies is therefore of central importance to contemporary bioscience. However, there are many technical, ethico-legal and scientific challenges to be overcome if an effective, valid, pooled analysis is to be achieved. Perhaps most critically, any data that are to be analysed in this way must be adequately 'harmonized'. This implies that the collection and recording of information and data must be done in a manner that is sufficiently similar in the different studies to allow valid synthesis to take place. METHODS: This conceptual article describes the origins, purpose and scientific foundations of the DataSHaPER (DataSchema and Harmonization Platform for Epidemiological Research; http://www.datashaper.org), which has been created by a multidisciplinary consortium of experts that was pulled together and coordinated by three international organizations: P³G (Public Population Project in Genomics), PHOEBE (Promoting Harmonization of Epidemiological Biobanks in Europe) and CPT (Canadian Partnership for Tomorrow Project). RESULTS: The DataSHaPER provides a flexible, structured approach to the harmonization and pooling of information between studies. Its two primary components, the 'DataSchema' and 'Harmonization Platforms', together support the preparation of effective data-collection protocols and provide a central reference to facilitate harmonization. The DataSHaPER supports both 'prospective' and 'retrospective' harmonization. CONCLUSION: It is hoped that this article will encourage readers to investigate the project further: the more the research groups and studies are actively involved, the more effective the DataSHaPER programme will ultimately be.
AU  - Fortier, I.*
AU  - Burton, P.R*
AU  - Robson, P.J.*
AU  - Ferretti, V.*
AU  - Little, J.*
AU  - L'Heureux, F.*
AU  - Deschenes, M.*
AU  - Knoppers, B.M.*
AU  - Doiron, D.*
AU  - Keers, J.C.*
AU  - Linksted, P.*
AU  - Harris, J.R.*
AU  - Lachance, G.*
AU  - Boileau, C.*
AU  - Pedersen, N.L.*
AU  - Hamilton, C.M.*
AU  - Hveem, K.*
AU  - Borugian, M.J.*
AU  - Gallagher, R.P.*
AU  - McLaughlin, J.*
AU  - Parker, L.*
AU  - Potter, J.D.*
AU  - Gallacher, J.*
AU  - Kaaks, R.*
AU  - Liu, B.*
AU  - Sprosen, T.*
AU  - Vilain, A.*
AU  - Atkinson, S.A.*
AU  - Rengifo, A.*
AU  - Morton, R.*
AU  - Metspalu, A.*
AU  - Wichmann, H.-E.
AU  - Tremblay, M.*
AU  - Chisholm, R.L.*
AU  - Garcia-Montero, A.*
AU  - Hillege, H.*
AU  - Litton, J.E.*
AU  - Palmer, L.J.*
AU  - Perola, M.*
AU  - Wolffenbuttel, B.H.R.*
AU  - Peltonen, L.*
AU  - Hudson, T.J.*
C1  - 4410
C2  - 28036
SP  - 1383-1393
TI  - Quality, quantity and harmony: The DataSHaPER approach to integrating data across bioclinical studies.
JO  - Int. J. Epidemiol.
VL  - 39
IS  - 5
PB  - Oxford Univ. Press
PY  - 2010
SN  - 0300-5771
ER  - 

TY  - JOUR
AB  - BACKGROUND: Meta-analysis of individual participant time-to-event data from multiple prospective epidemiological studies enables detailed investigation of exposure-risk relationships, but involves a number of analytical challenges. METHODS: This article describes statistical approaches adopted in the Emerging Risk Factors Collaboration, in which primary data from more than 1 million participants in more than 100 prospective studies have been collated to enable detailed analyses of various risk markers in relation to incident cardiovascular disease outcomes. RESULTS: Analyses have been principally based on Cox proportional hazards regression models stratified by sex, undertaken in each study separately. Estimates of exposure-risk relationships, initially unadjusted and then adjusted for several confounders, have been combined over studies using meta-analysis. Methods for assessing the shape of exposure-risk associations and the proportional hazards assumption have been developed. Estimates of interactions have also been combined using meta-analysis, keeping separate within- and between-study information. Regression dilution bias caused by measurement error and within-person variation in exposures and confounders has been addressed through the analysis of repeat measurements to estimate corrected regression coefficients. These methods are exemplified by analysis of plasma fibrinogen and risk of coronary heart disease, and Stata code is made available. CONCLUSION: Increasing numbers of meta-analyses of individual participant data from observational data are being conducted to enhance the statistical power and detail of epidemiological studies. The statistical methods developed here can be used to address the needs of such analyses.
AU  - Thompson, S.*
AU  - Kaptoge, S.*
AU  - White, I.*
AU  - Wood, A.*
AU  - Perry, P.*
AU  - Danesh, J.*
AU  - Emerging Risk Factors Collaboration (Döring, A.
AU  - Meisinger, C.)
C1  - 5541
C2  - 27578
SP  - 1345-1359
TI  - Statistical methods for the time-to-event analysis of individual participant data from multiple epidemiological studies.
JO  - Int. J. Epidemiol.
VL  - 39
IS  - 5
PB  - Oxford Univ. Press
PY  - 2010
SN  - 0300-5771
ER  - 

TY  - JOUR
AU  - Little, M.P.*
AU  - Tawn, E.J.*
AU  - Tzoulaki, I.*
AU  - Wakeford, R.*
AU  - Hildebrandt, G.*
AU  - Tapio, S.
AU  - Elliott, P.*
C1  - 289
C2  - 26276
SP  - 1159-1164
TI  - Comments: The non-cancer mortality experience of male workers at British Nuclear Fuels plc, 1946-2005.
JO  - Int. J. Epidemiol.
VL  - 38
IS  - 4
PB  - Oxford Univ Press
PY  - 2009
SN  - 0300-5771
ER  - 

TY  - JOUR
AB  - Background Within the framework of the multi-centre AIRGENE project we studied the association of the Mediterranean diet on plasma levels of various inflammatory markers, in myocardial infarction (MI) survivors from six geographic areas in Europe. Methods From 2003 to 2004, 1003 patients were repeatedly clinically examined. On every clinical visit (on average 5.8 times), blood EDTA-plasma samples were collected. High sensitivity C-reactive protein (CRP), interleukin (IL)-6 and fibrinogen concentrations were measured based on standardized procedures. Dietary habits were evaluated through a semi-quantitative Food Frequency Questionnaire (FFQ), whereas adherence to the Mediterranean diet was assessed by a diet score. Results A protective effect of adherence to the Mediterranean diet was found. For each unit of increasing adherence to the Mediterranean diet score there was a reduction of 3.1% in the average CRP levels (95% CI 0.5-5.7%) and of 1.9% in the average IL-6 levels (95% CI 0.5-3.4%) after adjusting for centre, age, sex, body mass index, physical activity, smoking status, diabetes and medication intake. No significant association was observed between the diet score and fibrinogen levels. Moderate intake of red wine (1-12 wine glasses per month) was associated with lower levels of CRP, IL-6 and fibrinogen. Conclusions Adherence to the traditional Mediterranean diet was associated with a reduction of the concentrations of inflammatory markers in MI survivors. This may, in part, explain the beneficial effects of this diet on various chronic diseases such as atherosclerosis and cancer, and expands its role to secondary prevention level.
AU  - Panagiotakos, D.B.*
AU  - Dimakopoulou, K.*
AU  - Katsouyanni, K.*
AU  - Bellander, T.*
AU  - Grau, M.*
AU  - Koenig, W.*
AU  - Lanki, T.*
AU  - Pistelli, R.*
AU  - Schneider, A.E.
AU  - Peters, A.
C1  - 1579
C2  - 26283
CY  - Oxford
SP  - 856-866
TI  - Mediterranean diet and inflammatory response in myocardial infarction survivors.
JO  - Int. J. Epidemiol.
VL  - 38
IS  - 3
PB  - Oxford Univ Press
PY  - 2009
SN  - 0300-5771
ER  - 

TY  - JOUR
AB  - BACKGROUND: The association of long-term air pollution and lung function has not been studied across adult European multi-national populations before. The aim of this study was to determine the association between long-term urban background air pollution and lung function levels, as well as change in lung function among European adults. METHODS: Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and the ratio thereof (FEV1/FVC) were assessed at baseline and after 9 years of follow-up in adults from 21 European centres (followed-up sample 5610). Fine particles (PM(2.5)) were measured in 2000/2001 using central monitors. RESULTS: Despite sufficient statistical power no significant associations were found between city-specific annual mean PM(2.5) and average lung function levels. The findings also do not support an effect on change in lung function, albeit statistical power was insufficient to significantly detect such an association. CONCLUSIONS: The inability to refuse the null hypothesis may reflect (i) no effect of urban air pollution on lung function or (ii) inherent biases due to the study design. Examples of the latter are lack of individual-level air quality assignment, not quantified within-city contrasts in traffic-related pollution, or the heterogeneity of the studied populations and their urban environments. Future studies on long-term effects of air pollution on lung function could increase statistical power and reduce potential misclassification and confounding by characterizing exposure on the level of individuals, capturing contrasts due to local sources, in particular traffic.
AU  - Götschi, T.*
AU  - Sunyer, J.*
AU  - Chinn, S.*
AU  - de Marco, R.*
AU  - Forsberg, B.*
AU  - Gauderman, J.W.*
AU  - García-Esteban, R.*
AU  - Heinrich, J.
AU  - Jacquemin, B.*
AU  - Jarvis, D.*
AU  - Ponzio, M.*
AU  - Villani, S.*
AU  - Künzli, N.*
C1  - 1384
C2  - 26118
SP  - 1349-1358
TI  - Air pollution and lung function in the European Community Respiratory Health Survey.
JO  - Int. J. Epidemiol.
VL  - 37
IS  - 6
PB  - Epub
PY  - 2008
SN  - 0300-5771
ER  - 

TY  - JOUR
AB  - Annoyance due to air pollution is a subjective score of air quality, which has been incorporated into the National Environmental monitoring of some countries. The objectives of this study are to describe the variations in annoyance due to air pollution in Europe and its individual and environmental determinants. METHODS: This study took place in the context of the European Community Respiratory Health Survey II (ECRHS II) that was conducted during 1999-2001. It included 25 centres in 12 countries and 7867 randomly selected adults from the general population. Annoyance due to air pollution was self-reported on an 11-point scale. Annual mean mass concentration of fine particles (PM(2.5)) and its sulphur (S) content were measured in 21 centres as a surrogate of urban air pollution. RESULTS: Forty-three per cent of participants reported moderate annoyance (1-5 on the scale) and 14% high annoyance (> or =6) with large differences across centres (2-40% of high annoyance). Participants in the Northern European countries reported less annoyance. Female gender, nocturnal dyspnoea, phlegm and rhinitis, self-reported car and heavy vehicle traffic in front of the home, high education, non-smoking and exposure to environmental tobacco smoke were associated with higher annoyance levels. At the centre level, adjusted means of annoyance scores were moderately associated with sulphur urban levels (slope 1.43 microg m(-3), standard error 0.40, r = 0.61). CONCLUSIONS: Annoyance due to air pollution is frequent in Europe. Individuals' annoyance may be a useful measure of perceived ambient quality and could be considered a complementary tool for health surveillance.
AU  - Jacquemin, B.*
AU  - Sunyer, J.*
AU  - Forsberg, B.*
AU  - Götschi, T.*
AU  - Bayer-Oglesby, L.*
AU  - Ackermann-Liebrich, U.*
AU  - de Marco, R.*
AU  - Heinrich, J.
AU  - Jarvis, D.*
AU  - Torén, K.*
AU  - Künzli, N.*
C1  - 3879
C2  - 24943
SP  - 809-820
TI  - Annoyance due to air pollution in Europe.
JO  - Int. J. Epidemiol.
VL  - 36
IS  - 4
PB  - Oxford Univ. Press
PY  - 2007
SN  - 0300-5771
ER  - 

TY  - JOUR
AU  - Peters, A.
C1  - 5118
C2  - 24009
SP  - 1355-1356
TI  - Commentary: Inflamed about ultrafine particles?
JO  - Int. J. Epidemiol.
VL  - 35
PY  - 2006
SN  - 0300-5771
ER  - 

TY  - JOUR
AB  - Background: Changes over time in inequalities in self-reported health are studied for increasingly more countries, but a comprehensive overview encompassing several countries is still lacking. The general aim of this article is to determine whether inequalities in self-assessed health in 10 European countries showed a general tendency either to increase or to decrease between the 1980s and the 1990s and whether trends varied among countries. Methods: Data were obtained from nationally representative interview surveys held in Finland, Sweden, Norway, Denmark, England, The Netherlands, West Germany, Austria, Italy, and Spain. The proportion of respondents with self-assessed health less than 'good' was measured in relation to educational level and income level. Inequalities were measured by means of age-standardized prevalence rates and odds ratios (ORs). Results: Socioeconomic inequalities in self-assessed health showed a high degree of stability in European countries. For all countries together, the ORs comparing low with high educational levels remained stable for men (2.61 in the 1980s and 2.54 in the 1990s) but increased slightly for women (from 2.48 to 2.70). The ORs comparing extreme income quintiles increased from 3.13 to 3.37 for men and from 2.43 to 2.86 for women. Increases could be demonstrated most clearly for Italian and Spanish men and women, and for Dutch women, whereas inequalities in health in the Nordic countries showed no tendency to increase. Conclusions: The results underscore the persistent nature of socioeconomic inequalities in health in modern societies. The relatively favourable trends in the Nordic countries suggest that these countries' welfare states were able to buffer many of the adverse effects of economic crises on the health of disadvantaged groups. © The Author 2004; all rights reserved.
AU  - Kunst, A.E.*
AU  - Bos, V.*
AU  - Lahelma, E.*
AU  - Bartley, M.*
AU  - Lissau, I.*
AU  - Regidor, E.*
AU  - Mielck, A.
AU  - Cardano, M.*
AU  - Dalstra, JA.*
AU  - Geurts, J.J.*
AU  - Helmert, U.*
AU  - Lennartsson, C.*
AU  - Ramm, J.*
AU  - Spadea, T.*
AU  - Stronegger, W.J.*
AU  - Mackenbach, J.P.*
C1  - 3355
C2  - 22748
SP  - 295-305
TI  - Trends in socioeconomic inequalities in self-assessed health in 10 European countries.
JO  - Int. J. Epidemiol.
VL  - 34
IS  - 2
PY  - 2005
SN  - 0300-5771
ER  - 

TY  - JOUR
AB  - Background Gender differences in the histological distribution of lung carcinoma and a possibly greater susceptibility of women than men to tobacco carcinogens, suggest a possible influence of sex-specific hormones. This study examines endocrine factors and risk of lung cancer among women by smoking status and histology.
      
      	Methods We used data of a case-control study on lung cancer conducted from 1990 to 1996 in Germany, including 811 histologically confirmed female cases and 912 female population controls. Information on various menstrual and reproductive factors, use of oral contraceptives (OC), hormone replacement therapy (HRT), and smoking was gathered through personal interviews using a structured questionnaire. Odds ratios (OR) and 95% CI adjusted for age, region, smoking, and education were calculated via logistic regression.
      
      	Results A reduction in lung cancer risk was observed with the use of OC (OR = 0.69; 95% CI: 0.51–0.92), but no trend in risk with increasing duration of use, age at first use, or calendar year of first use was present. A history of HRT was associated with a reduced risk (OR = 0.83; 95% CI: 0.64–1.09), particularly after long duration (⩾7 years) (OR = 0.59; 95% CI: 0.37–0.93). No clear association was found with regard to age at menarche, length of menstrual cycle, number of live-births, and age at menopause. Overall results did not differ much by histological cell subtype. The reduction in lung cancer risk associated with the use of exogenous hormones was primarily seen among smoking women.
      
      	Conclusions Our data provide evidence for a possible role of hormonal factors in the aetiology of lung cancer in women.
AU  - Kreuzer, M.*
AU  - Gerken, M.*
AU  - Heinrich, J.
AU  - Kreienbrock, L.*
AU  - Wichmann, H.-E.
C1  - 10134
C2  - 21620
SP  - 263-271
TI  - Hormonal factors and risk of lung cancer among woman?
JO  - Int. J. Epidemiol.
VL  - 32
PY  - 2003
SN  - 0300-5771
ER  - 

TY  - JOUR
AB  - BACKGROUND: The mode of inheritance of type 2 diabetes mellitus is still under discussion. Several studies have suggested an excess maternal transmission, however, more recent studies could not always confirm these findings. METHODS: We investigated the frequency of a maternal and paternal history of diabetes among diabetic and non-diabetic subjects and assessed the association between diabetes and a parental history of diabetes among participants of the MONICA Augsburg study. As an extension to previous studies, unknown parental status was taken into account. RESULTS: Of the 542 diabetic probands, 25.3% reported a positive maternal history of diabetes and 10.9% reported a positive paternal history of diabetes. Among the 12,209 non-diabetic participants a positive maternal history was also more common than a positive paternal history (12.5% versus 7.1%). Conversely, an unknown paternal status was more common than an unknown maternal status in both groups (diabetic subjects: 27.9% versus 16.8%, non-diabetic subjects: 16.8% versus 8.4%). Adjusted odds ratios (OR) for the association between a parental history of diabetes and diabetes status were similar for a positive maternal (OR = 2.9, 95% CI : 2.3-3.6) and paternal history (OR = 2.8, 95% CI : 2.1-3.8) and for an unknown maternal (OR = 1.3, 95% CI : 1.0-1.8) and paternal history (OR = 1.5, 95% CI : 1.2-1.9). CONCLUSION: Our findings do not support a strong excess maternal transmission of diabetes. Epidemiological biases and failure to account for 'don't know' responses may in part explain the previously observed predominance of a maternal history of diabetes.
AU  - Thorand, B.
AU  - Liese, A.D.*
AU  - Metzger, M.-H.
AU  - Reitmeir, P.
AU  - Schneider, A.E.
AU  - Löwel, H.
C1  - 24025
C2  - 31397
SP  - 1084-1089
TI  - Can inaccuracy of reported parental history of diabetes explain the maternal transmission hypothesis for diabetes?
JO  - Int. J. Epidemiol.
VL  - 30
IS  - 5
PB  - Oxford Univ. Press
PY  - 2001
SN  - 0300-5771
ER  - 

TY  - JOUR
AU  - Scherb, H.
AU  - Weigelt, E.
AU  - Brüske, I.
C1  - 21089
C2  - 19122
SP  - 932-940
TI  - European stillbirth proportions before and after the Chernobyl accident.
JO  - Int. J. Epidemiol.
VL  - 28
PY  - 1999
SN  - 0300-5771
ER  - 

TY  - JOUR
AB  - BACKGROUND: This paper describes morbidity differences according to occupational class among men from France, Switzerland, (West) Germany, Great Britain, the Netherlands, Denmark, and Sweden. METHODS: Data were obtained from national health interview surveys or similar surveys between 1986 and 1992. Four morbidity indicators were included. For each country, individual-level data on occupation were recorded according to one standard occupational class scheme: the Erikson-Goldthorpe social class scheme. To describe the pattern of morbidity by occupational class, odds ratios (OR) were calculated for each class using the average of the population as a reference. The size of morbidity differences was summarized by the OR of two broad hierarchical classes. All OR were age-adjusted. RESULTS: For all countries, a lower than average prevalence of morbidity was found for higher and lower administrators and professionals as well as for routine nonmanual workers, whereas a higher than average prevalence was found for skilled and unskilled manual workers and agricultural workers. Self-employed men were in general healthier than the average population. The relative health of farmers differed between countries. The morbidity difference between manual workers and the class of administrators and professionals was approximately equally large in all countries. Consistently larger inequality estimates, with no or slightly overlapping confidence intervals, were only found for Sweden in comparison with Germany. CONCLUSIONS: Thanks to the use of a common social class scheme in each country, a high degree of comparability was achieved. The results suggest that morbidity differences according to occupational class among men are very similar between different European countries.
AU  - Cavelaars, A.E.*
AU  - Kunst, A.E.*
AU  - Geurts, J.J.*
AU  - Helmert, U.*
AU  - Lundberg, O.*
AU  - Mielck, A.
AU  - Matheson, J.*
AU  - Mizrahi, A.*
AU  - Rasmussen, N.*
AU  - Spuhler, T.*
AU  - Mackenbach, J.P.*
C1  - 24157
C2  - 31445
SP  - 222-230
TI  - Morbidity differences by occupational class among men in seven European countries: An application of the Erikson-Goldthorpe social class scheme.
JO  - Int. J. Epidemiol.
VL  - 27
IS  - 2
PB  - Oxford Univ. Press
PY  - 1998
SN  - 0300-5771
ER  - 

TY  - JOUR
AB  - BACKGROUND: A review of studies on the association between childhood asthma and socioeconomic status (SES) in industrialized countries leads to the conclusion that there does not seem to be a clear association. A study from Aberdeen published 25 years ago, however, shows that among children with asthma, severe asthma is most prevalent in the lower social class, but this distinction between grades of asthma severity has been largely ignored since. METHODS: We screened all fourth grade schoolchildren of German nationality in Munich (4434 children, response rate 87 percent), distinguishing three severity grades in the same way as the study in Aberdeen. RESULTS: Prevalences of childhood asthma are reported by severity grade and SES. Prevalence of severe asthma was found to be significantly higher in the low as compared with the high socioeconomic group (Odds ratio = 2.37; 95 percent confidence interval: 1.28-4.41). This association could not be explained by established risk factors. CONCLUSIONS: More attention should be paid to the association between severe asthma and SES, with measures such as targeting early diagnosis and treatment towards low socioeconomic groups.
AU  - Mielck, A.
AU  - Reitmeir, P.
AU  - Wjst, M.
C1  - 24198
C2  - 31468
SP  - 388-393
TI  - Severity of childhood asthma by socioeconomic status.
JO  - Int. J. Epidemiol.
VL  - 25
IS  - 2
PB  - Oxford Univ. Press
PY  - 1996
SN  - 0300-5771
ER  - 

TY  - JOUR
AU  - Brenner, H.
AU  - Mielck, A.
C1  - 20581
C2  - 13790
SP  - 818-823
TI  - Children's Exposure to Parental Smoking in West Germany.
JO  - Int. J. Epidemiol.
VL  - 22
PY  - 1993
SN  - 0300-5771
ER  - 

TY  - JOUR
AU  - Stender, M.
AU  - Hense, H.-W.
AU  - Döring, A.
AU  - Keil, U.
C1  - 20449
C2  - 13655
SP  - 644-650
TI  - Physical Activity at Work and Cardiovascular Disease Risk. Results from the MONICA- Augsburg Study.
JO  - Int. J. Epidemiol.
VL  - 22
PY  - 1993
SN  - 0300-5771
ER  - 

TY  - JOUR
AU  - Hense, H.-W.
AU  - Filipiak, B.
AU  - Novak, L.
AU  - Stoeppler, M.
C1  - 19669
C2  - 12797
SP  - 753-762
TI  - Nonoccupational Determinants of Blood Lead Concentrations in a General Population.
JO  - Int. J. Epidemiol.
VL  - 21
PY  - 1992
SN  - 0300-5771
ER  - 

TY  - JOUR
AB  - We investigated the influence of various nonoccupational factors on blood lead levels (PbB) in a sample from the general population of southern Germany. Some 1703 men and 1661 women, aged 28-67 years, were examined in the first follow-up examination of the MONICA Augsburg cohort study in 1987-1988. Their mean PbB was 90 mg/l (SD: 35.9) for men and 65 mg/l (26.4) for women. Only 5% of the men and 1% of all women exceeded a PbB level of 150 mg/l indicating low-level lead exposure in this population. Blood lead was significantly associated with haematocrit values (P ' 0.001) and the shape of this association was curvilinear. Per gram of alcohol consumed, intake of beer had a lower impact on PbB than wine, presumably due to differential lead content in these alcoholic beverages. The alcohol-PbB associations were stronger for women than for men. The impact of smoking was generally moderate but again more prominent in women. In particular, the covariate adjusted odds ratios for women of childbearing age (28-47 years) to have PbB levels above 100 mg/l were 2.5 (95% confidence interval (CI): 1.3-4.7) for smoking versus nonsmoking females, 2.6 (95% CI: 6.0) for women drinking up to 40 g alcohol/day compared to abstainers, and 8.9 (95% CI: 3.2-25.1) for those drinking more than 40 g alcohol/day. Other factors like age, body mass, rural place of residence, and education or job position, had only minor influences on PbB. We conclude that haematocrit values should always be considered as potential confounders in low-level lead exposure research. High alcohol consumption and cigarette smoking are strongly related to elevated blood lead concentrations in the general population and may thereby convey additional health hazards such as impaired child development or blood pressure elevations. This deserves proper public health recognition.
AU  - Hense, H.W.
AU  - Filipiak, B.
AU  - Novak, L.R.
AU  - Stoeppler, M.
C1  - 40519
C2  - 0
SP  - 753-762
TI  - Nonoccupational determinants of blood lead concentrations in a general population.
JO  - Int. J. Epidemiol.
VL  - 21
IS  - 4
PY  - 1992
SN  - 0300-5771
ER  - 

TY  - JOUR
AU  - Jöckel, K.-H.
AU  - Ahrens, W.
AU  - Wichmann, H.-E.
AU  - Becher, H.
AU  - Bolm-Audorff, U.
AU  - Jahn, I.
AU  - Molik, B.
AU  - Greiser, E.
AU  - Timm, J.
C1  - 20521
C2  - 13731
SP  - 202-213
TI  - Occupational and Environmental Hazards Associated with Lung Cancer.
JO  - Int. J. Epidemiol.
VL  - 21
PY  - 1992
SN  - 0300-5771
ER  - 

TY  - JOUR
AU  - Sykes, D.H.
AU  - Haertel, U.
AU  - Gostautas, A.
AU  - Evans, A.E.
C1  - 20345
C2  - 13536
SP  - 1081-1089
TI  - The Framingham Type A Behaviour Pattern and Coronary Heart Disease in Three Countries: A  Cross-Cultural Comparison.
JO  - Int. J. Epidemiol.
VL  - 21
PY  - 1992
SN  - 0300-5771
ER  - 

TY  - JOUR
AU  - Chambless, L.
AU  - Döring, A.
AU  - Filipiak, B.
AU  - Keil, U.
C1  - 19724
C2  - 8733
SP  - 578-585
TI  - Determinants of HDL-Cholesterol and the HDL-Cholesterol/Total Cholesterol Ratio. Results of  the Lübeck Blood Pressure Study.
JO  - Int. J. Epidemiol.
VL  - 19
PY  - 1990
SN  - 0300-5771
ER  - 

TY  - JOUR
AB  - The WHO MONICA Project was designed to measure trends and determinants in cardiovascular disease mortality and coronary heart disease and cerebrovascular disease morbidity, and to assess the extent to which these trends are related to changes in known risk factors in 39 collaborative centres in 26 countries. Results of the baseline population surveys are presented. Use of standardized methods allows cross-sectional comparisons to be made of data from the 39 collaborating centres. The proportion of smokers varied between 34-62% among men and 3-52% among women. The median systolic blood pressure (SBP) values varied from 121 mmHg to 145 mmHg in men and from 117 mmHg to 143 mmHg in women. Median diastolic blood pressure (DBP) values varied from 74 mmHg to 91 mmHg in men and from 72 mmHg to 89 mmHg in women. The prevalence of actual hypertension, defined as SBP and/or DBP greater than 159/94 mmHg, or on antihypertensive medication, varied between 8.4% and 45.3% in men and between 12.6% and 40.5% in women. Median serum total cholesterol values varied from 4.1 mmol/l to 6.4 mmol/l in men and from 4.2 mmol/l to 6.4 mmol/l in women. The results show that there is a large variability in the risk-factor patterns among the MONICA populations. They also indicate that populations with low levels of risk factors are in the minority.
AU  - Keil, U.
AU  - Kuulasmaa, K.
C1  - 17915
C2  - 11074
SP  - 46-55
TI  - WHO Monica Project: Risk Factors.
JO  - Int. J. Epidemiol.
VL  - 18
PY  - 1989
SN  - 0300-5771
ER  - 

TY  - JOUR
AB  - Data from the Munich Blood Pressure Study I were used to investigate the distributions of fourth (D4) and fifth (D5) phase diastolic blood pressures in a population and to identify factors related to their difference. Muffling (in contrast to change of amplitude) of sounds was taken as the criterion for fourth phase Korotkoff sounds. D4 could not be detected (ie D4 = D5) in 33.7% of the 1032 men and in 42.1% of the 1163 women. The difference D4-D5 (mean±SEM) was 3.1±0.1 mmHg for male and 2.4±0.1 mmHg for female participants. Only 28% of D4-D5 differences were greater than 4 mmHg in men and 20.2% in women. D4-D5 varied considerably between the three measurements of each examination both related to participants and observers. Participant characteristics associated with greater D4-D5 were higher SBP, higher D4, and lower D5. Smoking was more common in men with greater D4-D5. Inter-observer variability was very strong. Non-detection of D4 ranged from 78.8% to 10.2% between observers. To assess the relative importance of participant and observer influence on the magnitude of D4-D5, we fitted a polychotomous logistic regression model. In this model, participant characteristics had only a weak effect on measured D4-D5. This was outweighed by potential observer effects several-fold stronger than the strongest participant effect. We conclude that for reliability reasons D5 should be given preference over D4 when measuring diastolic blood pressure in adults, whether for clinical or for epidemiological purposes.
AU  - Hense, H.W.
AU  - Stieber, J.
AU  - Chambless, L.E.
C1  - 41255
C2  - 36116
SP  - 513-518
TI  - Factors associated with measured differences between fourth and fifth phase diastolic blood pressure.
JO  - Int. J. Epidemiol.
VL  - 15
IS  - 4
PY  - 1986
SN  - 0300-5771
ER  -