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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Adiposity as a cause of cardiovascular disease: A Mendelian randomization study.
Int. J. Epidemiol. 44, 578-586 (2015)
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DOI
PMC
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.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Cardiovascular Disease ; Mendelian Randomization ; Body Mass Index ; Epidemiology; Body-mass Index; Multiple Genetic-variants; Incident Heart-failure; Ancient Origin; Blood-pressure; Obesity Gene; Risk; Association; Mortality; Metaanalysis
Sprache
englisch
Veröffentlichungsjahr
2015
HGF-Berichtsjahr
2015
ISSN (print) / ISBN
0300-5771
e-ISSN
1464-3685
Zeitschrift
International Journal of Epidemiology
Quellenangaben
Band: 44,
Heft: 2,
Seiten: 578-586
Verlag
Oxford University Press
Verlagsort
Oxford
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Epidemiology (EPI)
POF Topic(s)
30202 - Environmental Health
Forschungsfeld(er)
Genetics and Epidemiology
PSP-Element(e)
G-504091-004
PubMed ID
26016847
WOS ID
WOS:000357106100020
Scopus ID
84936753519
Erfassungsdatum
2015-05-30