title: Variants in ADCY5 and near CCNL1 are associated with fetal growth and birth weight.
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.
authors.affiliation: Genetics of Complex Traits, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter, UK.
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mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics*; D000483:Alleles; D001724:Birth Weight; D015331:Cohort Studies; D016213:Cyclins / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D005006:Ethnicity; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008297:Male; D008957:Models, Genetic; D011247:Pregnancy
chemical_list: C468873:CCNL1 protein, human; D016213:Cyclins; D007527:Isoenzymes; D000262:Adenylyl Cyclases; C419510:adenylyl cyclase type V; D005947:Glucose