Variants in ADCY5 and near CCNL1 are associated with fetal growth and birth weight
Date
2010
Authors
Freathy, R.
Mook-Kanamori, D.
Sovio, U.
Prokopenko, I.
Timpson, N.
Berry, D.
Warrington, N.
Widen, E.
Jan Hottenga, J.
Kaakinen, M.
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Journal article
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Nature Genetics, 2010; 42(5):430-435
Statement of Responsibility
Rachel M Freathy ... The Genetic Investigation of ANthropometric Traits (GIANT) Consortium ... The Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) ...The Wellcome Trust Case Control Consortium (WTCCC) ... Lyle J Palmer ... et al. for the Early Growth Genetics (EGG) Consortium.
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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 × 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 diabetes1, 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, 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 (Ptrend = 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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