Associations of genetic risk score with obesity and related traits and the modifying effect of physical activity in a Chinese Han population

PLoS One. 2014 Mar 13;9(3):e91442. doi: 10.1371/journal.pone.0091442. eCollection 2014.

Abstract

Background/objectives: Recent large-scale genome-wide association studies have identified multiple loci robustly associated with BMI, predominantly in European ancestry (EA) populations. However, associations of these loci with obesity and related traits have not been well described in Chinese Hans. This study aimed to investigate whether BMI-associated loci are, individually and collectively, associated with adiposity-related traits and obesity in Chinese Hans and whether these associations are modified by physical activity (PA).

Subjects/methods: We genotyped 28 BMI-associated single nucleotide polymorphisms (SNPs) in a population-based cohort including 2,894 unrelated Han Chinese. Genetic risk score (GRS), EA and East Asian ancestry (EAA) GRSs were calculated by adding BMI-increasing alleles based on all, EA and EAA identified SNPs, respectively. Interactions of GRS and PA were examined by including the interaction-term in the regression model.

Results: Individually, 26 of 28 SNPs showed directionally consistent effects on BMI, and associations of four loci (TMEM18, PCSK1, BDNF and MAP2K5) reached nominal significance (P<0.05). The GRS was associated with increased BMI, trunk fat and body fat percentages; and increased risk of obesity and overweight (all P<0.05). Effect sizes (0.11 vs. 0.17 kg/m2) and explained variance (0.90% vs. 1.45%) of GRS for BMI tended to be lower in Chinese Hans than in Europeans. The EA GRS and EAA GRS were associated with 0.11 and 0.13 kg/m2 higher BMI, respectively. In addition, we found that PA attenuated the effect of the GRS on BMI (Pinteraction = 0.022).

Conclusions: Our observations suggest that the combined effect of obesity-susceptibility loci on BMI tended to be lower in Han Chinese than in EA. The overall, EA and EAA GRSs exert similar effects on adiposity traits. Genetic predisposition to increased BMI is attenuated by PA in this population of Han Chinese.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiposity
  • Aged
  • Alleles
  • Asian Continental Ancestry Group
  • Body Mass Index
  • China
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Middle Aged
  • Models, Genetic
  • Motor Activity*
  • Obesity / ethnology
  • Obesity / genetics*
  • Polymorphism, Single Nucleotide*
  • Regression Analysis
  • Risk Factors

Grant support

The study was supported by the National High Technology Research and Development Program (863 Program 2009AA022704), the National Basic Research Program of China (973 Program 2012CB524900), the National Natural Science Foundation of China (30930081, 81170734 and 81021002), and the Chinese Academy of Sciences (KSCX2-EW-R-10 and SIBS2008006). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.