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Horikoshi, M.* ; Beaumont, R.N.* ; Day, F.R.* ; Warrington, N.M.* ; Kooijman, M.N.* ; Fernandez-Tajes, J.* ; Feenstra, B.* ; van Zuydam, N.R.* ; Gaulton, K.J.* ; Grarup, N.* ; Bradfield, J.P.* ; Strachan, D.P.* ; Li-Gao, R.* ; Ahluwalia, T.S.* ; Kreiner, E.* ; Rueedi, R.* ; Lyytikäinen, L.-P.* ; Cousminer, D.L.* ; Wu, Y.* ; Thiering, E. ; Wang, C.A.* ; Have, C.T.* ; Hottenga, J.J.* ; Vilor-Tejedor, N.* ; Joshi, P.K.* ; Boh, E.T.* ; Ntalla, I.* ; Pitkänen, N.* ; Mahajan, A.* ; van Leeuwen, E.M.* ; Joro, R.* ; Lagou, V.* ; Nodzenski, M.* ; Diver, L.A.* ; Zondervan, K.T.* ; Bustamante, M.* ; Marques-Vidal, P.* ; Mercader, J.M.* ; Bennett, A.J.* ; Rahmioglu, N.* ; Nyholt, D.R.* ; Ma, R.C.* ; Tam, C.H.* ; Tam, W.H.* ; Ganesh, S.K.* ; van Rooij, F.J.* ; Jones, S.E.* ; Loh, P.R.* ; Ruth, K.S.* ; Tuke, M.A.* ; Tyrrell, J.* ; Wood, A.R.* ; Yaghootkar, H.* ; Scholtens, D.M.* ; Paternoster, L.* ; Prokopenko, I.* ; Kovacs, P.* ; Atalay, M.* ; Willems, S.M.* ; Panoutsopoulou, K.* ; Wang, X.* ; Carstensen, L.* ; Geller, F.* ; Schraut, K.E.* ; Murcia, M.* ; van Beijsterveldt, C.E.* ; Willemsen, G.* ; Appel, E.V.* ; Fonvig, C.E.* ; Trier, C.* ; Tiesler, C.M. ; Standl, M. ; Kutalik, Z.* ; Bonàs-Guarch, S.* ; Hougaard, D.M.* ; Sánchez, F.* ; Torrents, D.* ; Waage, J.* ; Hollegaard, M.V.* ; de Haan, H.G.* ; Rosendaal, F.R.* ; Medina-Gomez, C.* ; Ring, S.M.* ; Hemani, G.* ; McMahon, G.* ; Robertson, N.R.* ; Groves, C.J.* ; Langenberg, C.* ; Luan, J.* ; Scott, R.A.* ; Zhao, J.H.* ; Mentch, F.D.* ; MacKenzie, S.M.* ; Reynolds, R.M.* ; Lowe, W.L.* ; Tönjes, A.* ; Stumvoll, M.* ; Lindi, V.* ; Lakka, T.A.* ; van Duijn, C.M.* ; Kiess, W.* ; Körner, A.* ; Sørensen, T.I.* ; Niinikoski, H.* ; Pahkala, K.* ; Raitakari, O.T.* ; Zeggini, E.* ; Dedoussis, G.V.* ; Teo, Y.Y.* ; Saw, S.M.* ; Melbye, M.* ; Campbell, H.* ; Wilson, J.F.* ; Vrijheid, M.* ; de Geus, E.J.* ; Boomsma, D.I.* ; Kadarmideen, H.N.* ; Holm, J.C.* ; Hansen, T.* ; Sebert, S.* ; Hattersley, A.T.* ; Beilin, L.J.* ; Newnham, J.P.* ; Pennell, C.E.* ; Heinrich, J. ; Adair, L.S.* ; Borja, J.B.* ; Mohlke, K.L.* ; Eriksson, J.G.* ; Widen, E.* ; Kähönen, M.* ; Viikari, J.S.* ; Lehtimäki, T.* ; Vollenweider, P.* ; Bønnelykke, K.* ; Bisgaard, H.* ; Mook-Kanamori, D.O.* ; Hofman, A.* ; Rivadeneira, F.* ; Uitterlinden, A.G.* ; Pisinger, C.* ; Pedersen, O.* ; Power, C.* ; Hyppönen, E.* ; Wareham, N.J.* ; Hakonarson, H.* ; Davies, E.* ; Walker, B.R.* ; Jaddoe, V.W.* ; Jarvelin, M.R.* ; Grant, S.F.* ; Vaag, A.A.* ; Lawlor, D.A.* ; Frayling, T.M.* ; Smith, G.D.* ; Morris, A.P.* ; Ong, K.K.* ; Felix, J.F.* ; Timpson, N.J.* ; Perry, J.R.* ; Evans, D.M* ; McCarthy, M.I.* ; Freathy, R.M.*

Genome-wide associations for birth weight and correlations with adult disease.

Nature 538, 248-252 (2016)
Postprint Research data DOI PMC
Open Access Green
Birth weight (BW) has been shown to be influenced by both fetal and maternal factors and in observational studies is reproducibly associated with future risk of adult metabolic diseases including type 2 diabetes (T2D) and cardiovascular disease. These life-course associations have often been attributed to the impact of an adverse early life environment. Here, we performed a multi-ancestry genome-wide association study (GWAS) meta-analysis of BW in 153,781 individuals, identifying 60 loci where fetal genotype was associated with BW (P < 5 × 10(-8)). Overall, approximately 15% of variance in BW was captured by assays of fetal genetic variation. Using genetic association alone, we found strong inverse genetic correlations between BW and systolic blood pressure (Rg = -0.22, P = 5.5 × 10(-13)), T2D (Rg = -0.27, P = 1.1 × 10(-6)) and coronary artery disease (Rg = -0.30, P = 6.5 × 10(-9)). In addition, using large -cohort datasets, we demonstrated that genetic factors were the major contributor to the negative covariance between BW and future cardiometabolic risk. Pathway analyses indicated that the protein products of genes within BW-associated regions were enriched for diverse processes including insulin signalling, glucose homeostasis, glycogen biosynthesis and chromatin remodelling. There was also enrichment of associations with BW in known imprinted regions (P = 1.9 × 10(-4)). We demonstrate that life-course associations between early growth phenotypes and adult cardiometabolic disease are in part the result of shared genetic effects and identify some of the pathways through which these causal genetic effects are mediated.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Blood-pressure; Altitude Adaptation; Genotype Imputation; Gene-expression; Human Height; Metaanalysis; Traits; Loci; Population; Variants
Language english
Publication Year 2016
HGF-reported in Year 2016
ISSN (print) / ISBN 0028-0836
e-ISSN 1476-4687
Journal Nature
Quellenangaben Volume: 538, Issue: 7624, Pages: 248-252 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology (EPI)
POF-Topic(s) 30503 - Chronic Diseases of the Lung and Allergies
Research field(s) Genetics and Epidemiology
PSP Element(s) G-503900-001
DOI 10.1038/nature19806
WOS ID WOS:000386671000046
Scopus ID 84991665514
PubMed ID 27680694
Erfassungsdatum 2016-10-13
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