title: The chromosome 3q25 genomic region is associated with measures of adiposity in newborns in a multi-ethnic genome-wide association study.
abstract: 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.
authors.affiliation: Division on Endocrinology, Metabolism and Molecular Medicine, Department of Medicine, University of Chicago, Chicago, IL 60637, USA. m-urbanek@northwestern.edu
authors.forename: Margrit
authors.initials: M
authors.lastname: Urbanek
authors.forename: M Geoffrey
authors.initials: MG
authors.lastname: Hayes
authors.forename: Loren L
authors.initials: LL
authors.lastname: Armstrong
authors.forename: Jean
authors.initials: J
authors.lastname: Morrison
authors.forename: Lynn P
authors.initials: LP
authors.lastname: Lowe
authors.forename: Sylvia E
authors.initials: SE
authors.lastname: Badon
authors.forename: Doug
authors.initials: D
authors.lastname: Scheftner
authors.forename: Anna
authors.initials: A
authors.lastname: Pluzhnikov
authors.forename: David
authors.initials: D
authors.lastname: Levine
authors.forename: Cathy C
authors.initials: CC
authors.lastname: Laurie
authors.forename: Caitlin
authors.initials: C
authors.lastname: McHugh
authors.forename: Christine M
authors.initials: CM
authors.lastname: Ackerman
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Mirel
authors.forename: Kimberly F
authors.initials: KF
authors.lastname: Doheny
authors.forename: Cong
authors.initials: C
authors.lastname: Guo
authors.forename: Denise M
authors.initials: DM
authors.lastname: Scholtens
authors.forename: Alan R
authors.initials: AR
authors.lastname: Dyer
authors.forename: Boyd E
authors.initials: BE
authors.lastname: Metzger
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Reddy
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Cox
authors.forename: William L
authors.initials: WL
authors.lastname: Lowe
mesh_terms: D050154:Adiposity / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D001724:Birth Weight / Q000235:genetics*; D044383:Black People / Q000235:genetics; D015992:Body Mass Index; D017691:Caribbean Region; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D015331:Cohort Studies; D016213:Cyclins / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D007231:Infant, Newborn; D016014:Linear Models; D008297:Male; D017058:Mexican Americans / Q000235:genetics; D011247:Pregnancy; D053491:Proteinase Inhibitory Proteins, Secretory / Q000235:genetics*; D044469:Racial Groups / Q000235:genetics*; D000074163:Serine Peptidase Inhibitor Kazal-Type 5; D013785:Thailand; D044465:White People / Q000235:genetics
chemical_list: C468873:CCNL1 protein, human; D016213:Cyclins; D053491:Proteinase Inhibitory Proteins, Secretory; C120650:SPINK5 protein, human; D000074163:Serine Peptidase Inhibitor Kazal-Type 5