Variants in ADCY5 and near CCNL1 are associated with fetal growth and birth weight
Freathy, RM; Mook-Kanamori, DO; Sovio, U; et al.Prokopenko, I; Timpson, NJ; Berry, DJ; Warrington, NM; Widen, E; Hottenga, JJ; Kaakinen, M; Lange, LA; Bradfield, JP; Kerkhof, M; Marsh, JA; Mägi, R; Chen, C-M; Lyon, HN; Kirin, M; Adair, LS; Aulchenko, YS; Bennett, AJ; Borja, JB; Bouatia-Naji, N; Charoen, P; Coin, LJM; Cousminer, DL; de Geus, EJC; Deloukas, P; Elliott, P; Evans, DM; Froguel, P; Genetic Investigation of ANthropometric Traits (GIANT) Consortium; Glaser, B; Groves, CJ; Hartikainen, A-L; Hassanali, N; Hirschhorn, JN; Hofman, A; Holly, JMP; Hyppönen, E; Kanoni, S; Knight, BA; Laitinen, J; Lindgren, CM; Meta-Analyses of Glucose and Insulin-related traits Consortium; McArdle, WL; O'Reilly, PF; Pennell, CE; Postma, DS; Pouta, A; Ramasamy, A; Rayner, NW; Ring, SM; Rivadeneira, F; Shields, BM; Strachan, DP; Surakka, I; Taanila, A; Tiesler, C; Uitterlinden, AG; van Duijn, CM; Wellcome Trust Case Control Consortium; Wijga, AH; Willemsen, G; Zhang, H; Zhao, J; Wilson, JF; Steegers, EAP; Hattersley, AT; Eriksson, JG; Peltonen, L; Mohlke, KL; Grant, SFA; Hakonarson, H; Koppelman, GH; Dedoussis, GV; Heinrich, J; Gillman, MW; Palmer, LJ; Frayling, TM; Boomsma, DI; Davey Smith, G; Power, C; Jaddoe, VWV; Jarvelin, M-R; Early Growth Genetics (EGG) Consortium; McCarthy, MI
Date: 1 May 2010
Nature Publishing Group
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 ...
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.
Institute of Biomedical & Clinical Science
College of Medicine and Health
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