Freathy, Rachel M; Mook-Kanamori, Dennis O; Sovio, Ulla; Prokopenko, Inga; Timpson, Nicholas J; Berry, Diane J; Warrington, Nicole M; Widen, Elisabeth; Hottenga, Jouke Jan; Kaakinen, Marika; +77 more... Lange, Leslie A; Bradfield, Jonathan P; Kerkhof, Marjan; Marsh, Julie A; Mägi, Reedik; Chen, Chih-Mei; Lyon, Helen N; Kirin, Mirna; Adair, Linda S; Aulchenko, Yurii S; Bennett, Amanda J; Borja, Judith B; Bouatia-Naji, Nabila; Charoen, Pimphen; Coin, Lachlan JM; Cousminer, Diana L; de Geus, Eco JC; Deloukas, Panos; Elliott, Paul; Evans, David M; Froguel, Philippe; Genetic Investigation of ANthropometric Traits (GIANT) Consortiu; Glaser, Beate; Groves, Christopher J; Hartikainen, Anna-Liisa; Hassanali, Neelam; Hirschhorn, Joel N; Hofman, Albert; Holly, Jeff MP; Hyppönen, Elina; Kanoni, Stavroula; Knight, Bridget A; Laitinen, Jaana; Lindgren, Cecilia M; Meta-Analyses of Glucose and Insulin-related traits Consortium; McArdle, Wendy L; O'Reilly, Paul F; Pennell, Craig E; Postma, Dirkje S; Pouta, Anneli; Ramasamy, Adaikalavan; Rayner, Nigel W; Ring, Susan M; Rivadeneira, Fernando; Shields, Beverley M; Strachan, David P; Surakka, Ida; Taanila, Anja; Tiesler, Carla; Uitterlinden, Andre G; van Duijn, Cornelia M; Wellcome Trust Case Control Consortium; Wijga, Alet H; Willemsen, Gonneke; Zhang, Haitao; Zhao, Jianhua; Wilson, James F; Steegers, Eric AP; Hattersley, Andrew T; Eriksson, Johan G; Peltonen, Leena; Mohlke, Karen L; Grant, Struan FA; Hakonarson, Hakon; Koppelman, Gerard H; Dedoussis, George V; Heinrich, Joachim; Gillman, Matthew W; Palmer, Lyle J; Frayling, Timothy M; Boomsma, Dorret I; Davey Smith, George; Power, Chris; Jaddoe, Vincent WV; Jarvelin, Marjo-Riitta; Early Growth Genetics (EGG) Consortium; McCarthy, Mark I; (2010) Variants in ADCY5 and near CCNL1 are associated with fetal growth and birth weight. Nature genetics, 42 (5). pp. 430-435. ISSN 1061-4036 DOI: https://doi.org/10.1038/ng.567
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Abstract
To identify genetic variants associated with birth weight, we meta-analyzed six genome-wide association (GWA) studies (n = 10,623 Europeans from pregnancy/birth cohorts) and followed up two lead signals in 13 replication studies (n = 27,591). rs900400 near LEKR1 and CCNL1 (P = 2 x 10(-35)) and rs9883204 in ADCY5 (P = 7 x 10(-15)) were robustly associated with birth weight. Correlated SNPs in ADCY5 were recently implicated in regulation of glucose levels and susceptibility to type 2 diabetes, providing evidence that the well-described association between lower birth weight and subsequent type 2 diabetes has a genetic component, distinct from the proposed role of programming by maternal nutrition. Using data from both SNPs, we found that the 9% of Europeans carrying four birth weight-lowering alleles were, on average, 113 g (95% CI 89-137 g) lighter at birth than the 24% with zero or one alleles (P(trend) = 7 x 10(-30)). The impact on birth weight is similar to that of a mother smoking 4-5 cigarettes per day in the third trimester of pregnancy.
Item Type | Article |
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Faculty and Department | Faculty of Epidemiology and Population Health > Dept of Non-Communicable Disease Epidemiology |
PubMed ID | 20372150 |
ISI | 277179500015 |
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