Variants in ADCY5 and near CCNL1 are associated with fetal growth and birth weight

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 thirteen replication studies (N=27,591). Rs900400 near LEKR1 and CCNL1 (P=2×10(−35)), and rs9883...

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Detalles Bibliográficos
Autores principales: 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, 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 J M, Cousminer, Diana L, de Geus, Eco J. C., Deloukas, Panos, Elliott, Paul, Evans, David M, Froguel, Philippe, Glaser, Beate, Groves, Christopher J, Hartikainen, Anna-Liisa, Hassanali, Neelam, Hirschhorn, Joel N, Hofman, Albert, Holly, Jeff M P, Hyppönen, Elina, Kanoni, Stavroula, Knight, Bridget A, Laitinen, Jaana, Lindgren, Cecilia M, 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, Wijga, Alet H, Willemsen, Gonneke, Zhang, Haitao, Zhao, Jianhua, Wilson, James F, Steegers, Eric A P, Hattersley, Andrew T, Eriksson, Johan G, Peltonen, Leena, Mohlke, Karen L, Grant, Struan F A, Hakonarson, Hakon, Koppelman, Gerard H, Dedoussis, George V, Heinrich, Joachim, Gillman, Matthew W, Palmer, Lyle J, Frayling, Timothy M, Boomsma, Dorret I, Smith, George Davey, Power, Chris, Jaddoe, Vincent W V, Jarvelin, Marjo-Riitta, McCarthy, Mark I
Formato: Texto
Lenguaje:English
Publicado: 2010
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2862164/
https://www.ncbi.nlm.nih.gov/pubmed/20372150
http://dx.doi.org/10.1038/ng.567
Descripción
Sumario: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 thirteen replication studies (N=27,591). Rs900400 near LEKR1 and CCNL1 (P=2×10(−35)), and rs9883204 in ADCY5 (P=7×10(−15)) were robustly associated with birth weight. Correlated SNPs in ADCY5 were recently implicated in regulation of glucose levels and type 2 diabetes susceptibility,1 providing evidence that the well described association between lower birth weight and subsequent type 2 diabetes2,3 has a genetic component, distinct from the proposed role of programming by maternal nutrition. Using data from both SNPs, the 9% of Europeans with 4 birth weight-lowering alleles were, on average, 113g (95%CI 89-137g) lighter at birth than the 24% with 0 or 1 allele (P(trend)=7×10(−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.4

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