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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.

SUBMITTER: Urbanek M

PROVIDER: S-EPMC3736865 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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

Urbanek Margrit M Hayes M Geoffrey MG Armstrong Loren L LL Morrison Jean J Lowe Lynn P LP Badon Sylvia E SE Scheftner Doug D Pluzhnikov Anna A Levine David D Laurie Cathy C CC McHugh Caitlin C Ackerman Christine M CM Mirel Daniel B DB Doheny Kimberly F KF Guo Cong C Scholtens Denise M DM Dyer Alan R AR Metzger Boyd E BE Reddy Timothy E TE Cox Nancy J NJ Lowe William L WL

Human molecular genetics 20130410 17

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 Stu ...[more]

PMID: 23575227

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Project description:ObjectivesThis study sought to compare various measures of adiposity with risk for incident hospitalized heart failure (HF) with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF).BackgroundObesity is a risk factor for HF, particularly HFpEF. It is unknown which measures of adiposity, including anthropometrics and computed tomography (CT)-measured fat area, are most predictive of HF subtypes.MethodsThe authors studied 1,806 participants of the MESA (Multi-Ethnic Study of Atherosclerosis) study without baseline cardiovascular disease who underwent anthropometrics (body mass index [BMI] and waist circumference) and an abdominal CT. Subcutaneous and visceral adipose tissue (VAT) were measured from a single CT slice at L2-L3. Cox hazard models were used to examine associations of adiposity with incident hospitalized HFpEF and HFrEF events. Fully adjusted models included demographics, HF risk factors, and N-terminal pro-B-type natriuretic peptide.ResultsOver a mean follow-up of 11 years, there were 34 HFpEF and 36 HFrEF events. The fully adjusted hazard ratio (95% confidence interval [CI]) per 1-SD higher of each anthropometric and CT-measured adiposity measures for incident HFpEF were as follows: BMI HR: 1.66; 95% CI: 1.12 to 2.45; waist circumference HR: 1.59; 95% CI: 1.05 to 2.40; and VAT HR: 2.24; 95% CI: 1.44 to 3.49. None of these adiposity measures were associated with HFrEF. Even among overweight/obese adults (BMI ≥25 kg/m2), assessment of VAT (per 1-SD) was strongly associated with HFpEF (HR: 2.78; 95% CI: 1.62 to 4.76). Subcutaneous adipose tissue was neither associated with HFpEF nor HFrEF.ConclusionsIn a multiethnic cohort free of cardiovascular disease, CT-measured VAT was independently associated with incident hospitalized HFpEF but not HFrEF. Measuring visceral fat at the time of CT imaging for other indications may offer additional prognostication of HF risk. (Multi-Ethnic Study of Atherosclerosis [MESA]; NCT00005487).

Dataset Information

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

Publications

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

Similar Datasets

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