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

Nat Genet. 2010 May;42(5):430-5. doi: 10.1038/ng.567. Epub 2010 Apr 6.

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.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylyl Cyclases / genetics*
  • Alleles
  • Birth Weight
  • Cohort Studies
  • Cyclins / genetics*
  • Diabetes Mellitus, Type 2 / genetics
  • Ethnic Groups
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Glucose / metabolism
  • Humans
  • Isoenzymes / genetics*
  • Male
  • Models, Genetic
  • Pregnancy

Substances

  • CCNL1 protein, human
  • Cyclins
  • Isoenzymes
  • Adenylyl Cyclases
  • adenylyl cyclase type V
  • Glucose

Grant support