Genome-wide associations for birth weight and correlations with adult disease
Creators: name: Standl, Marie
name: Grarup, Niels
name: Mercader, Josep M.
name: Nodzenski, Michael
name: Warrington, Nicole M.
name: Felix, Janine F.
name: Tuke, Marcus A.
name: Hofman, Albert
name: Mohlke, Karen L.
name: Strachan, David P.
name: Kadarmideen, Haja N.
name: Bonàs-Guarch, Sílvia
name: Scholtens, Denise M.
name: Panoutsopoulou, Kalliope
name: Kovacs, Peter
name: Li-Gao, Ruifang
name: Langenberg, Claudia
name: Bønnelykke, Klaus
name: Morris, Andrew P.
name: Reynolds, Rebecca M.
name: Sørensen, Thorkild I. A.
name: Day, Felix R.
name: Freathy, Rachel M.
name: Schraut, Katharina E.
name: Feenstra, Bjarke
name: Bisgaard, Hans
name: Torrents, David
name: Carstensen, Lisbeth
name: De Haan, Hugoline G.
name: Newnham, John P.
name: Ruth, Katherine S.
name: Ring, Susan M.
name: Sánchez, Friman
name: Pisinger, Charlotta
name: Bustamante, Mariona
name: Robertson, Neil R.
name: Rahmioglu, Nilufer
name: Kutalik, Zoltán
name: Rueedi, Rico
name: Boomsma, Dorret I.
name: Horikoshi, Momoko
name: Rosendaal, Frits R.
name: Van Beijsterveldt, Catharina E. M.
name: Campbell, Harry
name: Mentch, Frank D.
name: Kreiner, Eskil
name: Stumvoll, Michael
name: Fonvig, Cilius E.
name: Willems, Sara M.
name: Willemsen, Gonneke
name: Prokopenko, Inga
name: Beaumont, Robin N.
name: Wu, Ying
name: Geller, Frank
name: Smith, George Davey
name: Bennett, Amanda J.
name: Pitkänen, Niina
name: Dedoussis, George V.
name: Vilor-Tejedor, Natalia
name: Lindi, Virpi
name: Jones, Samuel E.
name: Trier, Caecilie
name: Tam, Claudia H. T.
name: Vrijheid, Martine
name: Pedersen, Oluf
name: Tyrrell, Jessica
name: Widén, Elisabeth
name: Wareham, Nicholas J.
name: Boh, Eileen Tai Hui
name: Uitterlinden, André G.
name: De Geus, Eco J. C. N.
name: Mahajan, Anubha
name: Kiess, Wieland
name: Vaag, Allan A.
name: Wang, Carol A.
name: Ganesh, Santhi K.
name: Eriksson, Johan G.
name: Van Leeuwen, Elisabeth M.
name: Ong, Ken K.
name: Timpson, Nicholas J.
name: Luan, Jian'An
name: Murcia, Mario
name: Hottenga, Jouke-Jan
name: Van Rooij, Frank J. A.
name: Thiering, Elisabeth
name: Mook-Kanamori, Dennis O.
name: Davies, Eleanor
name: Van Zuydam, Natalie R.
name: Ntalla, Ioanna
name: Vollenweider, Peter
name: Zhao, Jing Hua
name: Sebert, Sylvain
name: Hakonarson, Hakon
name: Walker, Brian R.
name: Appel, Emil V. R.
name: Joshi, Peter K.
name: Tönjes, Anke
name: Adair, Linda S.
name: Lakka, Timo A.
name: Have, Christian T.
name: Körner, Antje
name: Nyholt, Dale R.
name: McMahon, George
name: Jaddoe, Vincent W. V.
name: Tam, Wing Hung
name: Tiesler, Carla M. T.
name: Teo, Yik-Ying
name: Atalay, Mustafa
name: Raitakari, Olli T.
name: Niinikoski, Harri
name: Paternoster, Lavinia
name: Melbye, Mads
name: Rivadeneira, Fernando
name: Kähönen, Mika
name: Bradfield, Jonathan P.
name: Beilin, Lawrence J.
name: Hyppönen, Elina
name: Loh, Po-Ru
name: Wood, Andrew R.
name: Ma, Ronald C. W.
name: Scott, Robert A.
name: Viikari, Jorma S.
name: Medina-Gomez, Carolina
name: Pahkala, Katja
name: Hansen, Torben
name: Wilson, James F.
name: Zeggini, Eleftheria
name: Kooijman, Marjolein N.
name: Joro, Raimo
name: Cousminer, Diana L.
name: Borja, Judith B.
name: Frayling, Timothy M.
name: Järvelin, Marjo-Riitta
name: Perry, John R. B.
name: Holm, Jens-Christian
name: Lagou, Vasiliki
name: MacKenzie, Scott M.
name: Fernandez-Tajes, Juan
name: Evans, David M.
name: Pennell, Craig E.
name: McCarthy, Mark I.
name: Waage, Johannes
name: Heinrich, Joachim
name: Ahluwalia, Tarunveer S.
name: Grant, Struan F. A.
name: Hemani, Gibran
name: Lawlor, Debbie A.
name: Lehtimäki, Terho
name: Van Duijn, Cornelia M.
name: Gaulton, Kyle J.
name: Zondervan, Krina T.
name: Lyytikaïnen, Leo-Pekka
name: Hollegaard, Mads V.
name: Wang, Xu
name: Lowe, William L.
name: Yaghootkar, Hanieh
name: Diver, Louise A.
name: Hattersley, Andrew T.
name: Groves, Christopher J.
name: Hougaard, David M.
name: Power, Christine
name: Marques-Vidal, Pedro
name: Saw, Seang-Mei
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2016

description: Birth weight (BW) is influenced by both foetal and maternal factors and in observational studies is reproducibly associated with future risk of adult metabolic diseases including type 2 diabetes (T2D) and cardiovascular disease1. These lifecourse associations have often been attributed to the impact of an adverse early life environment. We performed a multi-ancestry genome-wide association study (GWAS) meta-analysis of BW in 153,781 individuals, identifying 60 loci where foetal genotype was associated with BW (P <5x10-8). Overall, ˜15% of variance in BW could be captured by assays of foetal genetic variation. Using genetic association alone, we found strong inverse genetic correlations between BW and systolic blood pressure (rg-0.22, P =5.5x10-13), T2D (rg-0.27, P =1.1x10-6) and coronary artery disease (rg-0.30, P =6.5x10-9) and, in large cohort data sets, 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 =1.9x10-4). We have demonstrated that lifecourse associations between early growth phenotypes and adult cardiometabolic disease are in part the result of shared genetic effects and have highlighted some of the pathways through which these causal genetic effects are mediated.