title: Genetic risk score for prediction of newborn adiposity and large-for-gestational-age birth.
abstract: BACKGROUND
  Macrosomic infants are at increased risk for adverse metabolic outcomes. Improving prediction of large-for-gestational-age (LGA) birth may help prevent these outcomes.
  
  
  OBJECTIVE
  This study sought to determine whether genes associated with obesity-related traits in adults are associated with newborn size, and whether a genetic risk score (GRS) predicts LGA birth.
  
  
  METHODS
  Single nucleotide polymorphisms (SNPs) in 40 regions associated with adult obesity-related traits were tested for association with newborn size. GRS's for birth weight and sum of skinfolds (SSF) specific to ancestry were calculated using the most highly associated SNP for each ancestry in genomic regions with one or more SNPs associated with birth weight and/or SSF in at least one ancestry group or meta-analyses.
  
  
  METHODS
  Newborns from the Hyperglycemia Adverse Pregnancy Outcomes Study were studied (942 Afro-Caribbean, 1294 Northern European, 573 Mexican-American, and 1182 Thai).
  
  
  METHODS
  Birth weight >90th percentile (LGA) and newborn SSF >90th percentile were primary outcomes.
  
  
  RESULTS
  After adjustment for ancestry, sex, gestational age at delivery, parity, maternal genotype, maternal smoking/alcohol intake, age, body mass index, height, blood pressure and glucose, 25 and 23 SNPs were associated (P < .001) with birth weight and newborn SSF, respectively. The GRS was highly associated with both phenotypes as continuous variables across all ancestries (P ≤ 1.6 × 10(-19)) and improved prediction of birth weight and SSF >90th percentile when added to a baseline model incorporating the covariates listed above.
  
  
  CONCLUSIONS
  A GRS comprised of SNPs associated with adult obesity-related traits may provide an approach for predicting LGA birth and newborn adiposity beyond established risk factors.
authors.affiliation: Division of Pediatric Endocrinology, Ann & Robert H. Lurie Children's Hospital of Chicago (R.C.), Department of Preventive Medicine (S.E.B., J.R., A.C.R., L.P.L., D.M.S.), Division of Endocrinology, Metabolism & Molecular Medicine (L.L.A., M.U., B.E.M., M.G.H., W.L.L.), Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611; and PhD (cand) (S.B.), University of Washington, Seattle, Washington 355852.
authors.forename: Reeti
authors.initials: R
authors.lastname: Chawla
authors.forename: Sylvia E
authors.initials: SE
authors.lastname: Badon
authors.forename: Janani
authors.initials: J
authors.lastname: Rangarajan
authors.forename: Anna C
authors.initials: AC
authors.lastname: Reisetter
authors.forename: Loren L
authors.initials: LL
authors.lastname: Armstrong
authors.forename: Lynn P
authors.initials: LP
authors.lastname: Lowe
authors.forename: Margrit
authors.initials: M
authors.lastname: Urbanek
authors.forename: Boyd E
authors.initials: BE
authors.lastname: Metzger
authors.forename: M Geoffrey
authors.initials: MG
authors.lastname: Hayes
authors.forename: Denise M
authors.initials: DM
authors.lastname: Scholtens
authors.forename: William L
authors.initials: WL
authors.lastname: Lowe
mesh_terms: D050154:Adiposity / Q000235:genetics*; D000328:Adult; D000483:Alleles; D001724:Birth Weight; D005260:Female; D005320:Fetal Macrosomia / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009765:Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy