Dataset Information

Penetrance of Polygenic Obesity Susceptibility Loci across the Body Mass Index Distribution.

ABSTRACT: A growing number of single-nucleotide polymorphisms (SNPs) have been associated with body mass index (BMI) and obesity, but whether the effects of these obesity-susceptibility loci are uniform across the BMI distribution remains unclear. We studied the effects of 37 BMI-associated SNPs in 75,230 adults of European ancestry across BMI percentiles by using conditional quantile regression (CQR) and meta-regression (MR) models. The effects of nine SNPs (24%)-rs1421085 (FTO; p = 8.69 × 10-15), rs6235 (PCSK1; p = 7.11 × 10-6), rs7903146 (TCF7L2; p = 9.60 × 10-6), rs11873305 (MC4R; p = 5.08 × 10-5), rs12617233 (FANCL; p = 5.30 × 10-5), rs11672660 (GIPR; p = 1.64 × 10-4), rs997295 (MAP2K5; p = 3.25 × 10-4), rs6499653 (FTO; p = 6.23 × 10-4), and rs3824755 (NT5C2; p = 7.90 × 10-4)-increased significantly across the sample BMI distribution. We showed that such increases stemmed from unadjusted gene interactions that enhanced the effects of SNPs in persons with a high BMI. When 125 height-associated SNPs were analyzed for comparison, only one (<1%), rs6219 (IGF1, p = 1.80 × 10-4), showed effects that varied significantly across height percentiles. Cumulative gene scores of these SNPs (GS-BMI and GS-height) showed that only GS-BMI had effects that increased significantly across the sample distribution (BMI: p = 7.03 × 10-37; height: p = 0.499). Overall, these findings underscore the importance of gene-gene and gene-environment interactions in shaping the genetic architecture of BMI and advance a method for detecting such interactions by using only the sample outcome distribution.

SUBMITTER: Abadi A

PROVIDER: S-EPMC5812888 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Penetrance of Polygenic Obesity Susceptibility Loci across the Body Mass Index Distribution.

Abadi Arkan A Alyass Akram A Robiou du Pont Sebastien S Bolker Ben B Singh Pardeep P Mohan Viswanathan V Diaz Rafael R Engert James C JC Yusuf Salim S Gerstein Hertzel C HC Anand Sonia S SS Meyre David D

American journal of human genetics 20171201 6

A growing number of single-nucleotide polymorphisms (SNPs) have been associated with body mass index (BMI) and obesity, but whether the effects of these obesity-susceptibility loci are uniform across the BMI distribution remains unclear. We studied the effects of 37 BMI-associated SNPs in 75,230 adults of European ancestry across BMI percentiles by using conditional quantile regression (CQR) and meta-regression (MR) models. The effects of nine SNPs (24%)-rs1421085 (FTO; p = 8.69 × 10<sup>-15</su ...[more]

PMID: 29220676

Similar Datasets

Project description:BackgroundAccurate obesity classification is important so that appropriate intervention can be instituted to modify metabolic risk factors. Commonly utilized body mass index (BMI) and percentage body fat (PBF) are influenced by lean mass whereas fat mass index (FMI) measures only body fat. This study compares the prevalence of obesity and metabolic risk factors with FMI, BMI and PBF using DXA (dual-energy x-ray absorptiometry).Methods489 women randomly recruited from the electoral roll were stratified into 4 age groups; 40-49, 50-59, 60-69 and 70-79 years from 2000 to 2001. Clinical data and DXA body composition were obtained. Statistical analyses were performed using Medcalc v15 (Ostend, Belgium) with significance level at p = 0.05 (two-tailed).ResultsThere was higher prevalence of obesity using PBF compared to BMI and FMI (p<0.001). This difference was greater from age 50-59 (p<0.05) which may be explained by age-related lean mass loss. PBF over-classified obesity in over 35% of normal and 95% of overweight categories compared to FMI and BMI. BMI has a sensitivity of 78.9% and specificity of 98.3% for obesity using FMI as the standard. BMI under-classified obesity in the overweight category by 14.9% compared to FMI. There was no difference in diabetes, dyslipidemia, hypertension and metabolic syndrome prevalence within the BMI-obesity and FMI-obesity categories (p>0.05).ConclusionPBF classified more obesity than BMI and FMI because of its low pre-determined threshold. The greater difference with PBF compared to BMI and FMI from the 50-59 decade onwards can be attributed to age-related lean mass loss. BMI had the lowest sensitivity for obesity diagnosis. BMI under-classified obesity in the overweight category compared to FMI due to its inability to differentiate lean mass. However, there was no significant difference in the prevalence of metabolic risk factors between BMI and FMI-obesity categories indicating that fat location may influence metabolic dysregulation.

Dataset Information

Penetrance of Polygenic Obesity Susceptibility Loci across the Body Mass Index Distribution.

Publications

Penetrance of Polygenic Obesity Susceptibility Loci across the Body Mass Index Distribution.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets