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

Journal article

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.

Authors: Freathy, R; Mook-Kanamori, DO; Sovio, U; Prokopenko, I; Timpson, N

• Publication status: Published
• Journal: Nature genetics
• Volume: 42
• Issue: 5
• Pages: 430-435
• Publication date: 2010-05-01
• DOI: 10.1038/ng.567
• EISSN: 1546-1718
• ISSN: 1061-4036
• Language: English
• Keywords: Genetic Investigation of ANthropometric Traits (GIANT) Consortium; Early Growth Genetics (EGG) Consortium; Humans; Models, Genetic; Cyclins; Ethnic Groups; Cohort Studies; Glucose; Wellcome Trust Case Control Consortium; Isoenzymes; Pregnancy; Meta-Analyses of Glucose and Insulin-related traits Consortium; Diabetes Mellitus, Type 2; Birth Weight; Genotype; Female; Alleles; Male; Genetic Predisposition to Disease; Adenylate Cyclase