The chromosome 3q25 genomic region is associated with measures of adiposity in newborns in a multi-ethnic genome-wide association study.

Journal Article (Journal Article;Multicenter Study)

Newborns characterized as large and small for gestational age are at risk for increased mortality and morbidity during the first year of life as well as for obesity and dysglycemia as children and adults. The intrauterine environment and fetal genes contribute to the fetal size at birth. To define the genetic architecture underlying the newborn size, we performed a genome-wide association study (GWAS) in 4281 newborns in four ethnic groups from the Hyperglycemia and Adverse Pregnancy Outcome Study. We tested for association with newborn anthropometric traits (birth length, head circumference, birth weight, percent fat mass and sum of skinfolds) and newborn metabolic traits (cord glucose and C-peptide) under three models. Model 1 adjusted for field center, ancestry, neonatal gender, gestational age at delivery, parity, maternal age at oral glucose tolerance test (OGTT); Model 2 adjusted for Model 1 covariates, maternal body mass index (BMI) at OGTT, maternal height at OGTT, maternal mean arterial pressure at OGTT, maternal smoking and drinking; Model 3 adjusted for Model 2 covariates, maternal glucose and C-peptide at OGTT. Strong evidence for association was observed with measures of newborn adiposity (sum of skinfolds model 3 Z-score 7.356, P = 1.90×10⁻¹³, and to a lesser degree fat mass and birth weight) and a region on Chr3q25.31 mapping between CCNL and LEKR1. These findings were replicated in an independent cohort of 2296 newborns. This region has previously been shown to be associated with birth weight in Europeans. The current study suggests that association of this locus with birth weight is secondary to an effect on fat as opposed to lean body mass.

Full Text

Duke Authors

Cited Authors

  • Urbanek, M; Hayes, MG; Armstrong, LL; Morrison, J; Lowe, LP; Badon, SE; Scheftner, D; Pluzhnikov, A; Levine, D; Laurie, CC; McHugh, C; Ackerman, CM; Mirel, DB; Doheny, KF; Guo, C; Scholtens, DM; Dyer, AR; Metzger, BE; Reddy, TE; Cox, NJ; Lowe, WL; HAPO Study Cooperative Research Group,

Published Date

  • September 1, 2013

Published In

Volume / Issue

  • 22 / 17

Start / End Page

  • 3583 - 3596

PubMed ID

  • 23575227

Pubmed Central ID

  • PMC3736865

Electronic International Standard Serial Number (EISSN)

  • 1460-2083

Digital Object Identifier (DOI)

  • 10.1093/hmg/ddt168


  • eng

Conference Location

  • England