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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.

Original publication

DOI

10.1038/ng.567

Type

Journal article

Journal

Nature genetics

Publication Date

05/2010

Volume

42

Pages

430 - 435

Addresses

Genetics of Complex Traits, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter, UK.

Keywords

Genetic Investigation of ANthropometric Traits (GIANT) Consortium, Meta-Analyses of Glucose and Insulin-related traits Consortium, Wellcome Trust Case Control Consortium, Early Growth Genetics (EGG) Consortium, Humans, Diabetes Mellitus, Type 2, Genetic Predisposition to Disease, Birth Weight, Isoenzymes, Glucose, Cyclins, Cohort Studies, Pregnancy, Genotype, Alleles, Models, Genetic, Ethnic Groups, Female, Male, Adenylyl Cyclases