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 × 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 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, 113g (95% CI 89-137g) lighter at birth than the 24% with zero or one alleles (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.

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Persistent URL dx.doi.org/10.1038/ng.567, hdl.handle.net/1765/28299
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Freathy, R.M., Mook-Kanamori, D.O., Sovio, U., Prokopenko, I., Timpson, N., Berry, D., … McCarthy, M.I.. (2010). Variants in ADCY5 and near CCNL1 are associated with fetal growth and birth weight. Nature Genetics, 42(5), 430–435. doi:10.1038/ng.567