title: Associations of genetic risk score with obesity and related traits and the modifying effect of physical activity in a Chinese Han population.
abstract: OBJECTIVE
  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).
  
  
  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.
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate University of the Chinese Academy of Sciences, Shanghai, People's Republic of China.
authors.forename: Jingwen
authors.initials: J
authors.lastname: Zhu
authors.affiliation: The Charles Bronfman Institute for Personalized Medicine, The Mindich Child Health and Development Institute, The Genetics of Obesity and Related Metabolic Traits Program, Department of Preventive Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Ruth J F
authors.initials: RJ
authors.lastname: Loos
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate University of the Chinese Academy of Sciences, Shanghai, People's Republic of China.
authors.forename: Ling
authors.initials: L
authors.lastname: Lu
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate University of the Chinese Academy of Sciences, Shanghai, People's Republic of China.
authors.forename: Geng
authors.initials: G
authors.lastname: Zong
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate University of the Chinese Academy of Sciences, Shanghai, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Gan
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate University of the Chinese Academy of Sciences, Shanghai, People's Republic of China.
authors.forename: Xingwang
authors.initials: X
authors.lastname: Ye
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate University of the Chinese Academy of Sciences, Shanghai, People's Republic of China.
authors.forename: Liang
authors.initials: L
authors.lastname: Sun
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate University of the Chinese Academy of Sciences, Shanghai, People's Republic of China.
authors.forename: Huaixing
authors.initials: H
authors.lastname: Li
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate University of the Chinese Academy of Sciences, Shanghai, People's Republic of China.
authors.forename: Xu
authors.initials: X
authors.lastname: Lin
mesh_terms: D050154:Adiposity; D000368:Aged; D000483:Alleles; D044466:Asian People; D015992:Body Mass Index; D002681:China; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D008957:Models, Genetic; D009043:Motor Activity; D009765:Obesity / Q000208:ethnology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012044:Regression Analysis; D012307:Risk Factors