Variants in ADCY5 and near CCNL1 Are Associated with Fetal Growth and Birth Weight

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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, et al. (2010). Variants in ADCY5 and near CCNL1 Are Associated with Fetal Growth and Birth Weight. Nature Genetics, 42(5), 430-435. PMCID: PMC2862164

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.

URL

http://dx.doi.org/10.1038/ng.567

Reference Type

Journal Article

Year Published

2010

Journal Title

Nature Genetics

Author(s)

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
The Genetic Investigation of ANthropometric Traits (GIANT) Consortium,
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.
The Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC),
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 M. T.
Uitterlinden, Andre G.
van Duijn, Cornelia M.
The Wellcome Trust Case Control Consortium (WTCCC),
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
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., for the Early Growth Genetics (EGG) Consortium,

PMCID

PMC2862164

ORCiD

Adair - 0000-0002-3670-8073