Obesity susceptibility genetic variants identified from recent genome-wide association studies: implications in a chinese population

J Clin Endocrinol Metab. 2010 Mar;95(3):1395-403. doi: 10.1210/jc.2009-1465. Epub 2010 Jan 8.

Abstract

Context: Recent large-scale genome-wide association studies identified novel genetic variants associated with obesity and body mass index (BMI) in addition to the well-described FTO and MC4R genetic variants.

Objective: This study aimed to examine 13 previously reported obesity and/or BMI-associated loci for associations with obesity in Chinese.

Design and study participants: This was a cross-sectional case-control study in 470 obese cases (BMI > or =27.5 kg/m(2)) and 700 normal-weight controls (18.5 < or = BMI < or = 23.0 kg/m(2)).

Results: A significant association with obesity could be replicated (one tailed P < 0.05) in seven of the 13 single-nucleotide polymorphisms (SNPs) in the case-control study. These included GNPDA2 rs10938397 (P = 7.3 x 10(-4)); FTO rs8050136 (P = 8 x 10(-4)); MC4R rs17782313 (P = 1.2 x 10(-3)); KCTD15 rs29941 (P = 8 x 10(-3)); SFRS10-ETV5-DGKG rs7647305 (P = 0.023); SEC16B-RASAL2 rs10913469 (P = 0.041); and NEGR1 rs3101336 (P = 0.046). Combined genetic risk scores were calculated, and we observed ORs ranging from 1.17 to 1.23 for each unit increase in the genetic risk scores. Associations with obesity-related quantitative traits were analyzed separately for cases and controls. KCTD15 SNP rs29941 (P = 1 x 10(-3)) was significantly associated with fasting glucose in the control group, whereas only the FTO SNP rs8050136 was associated with BMI (P = 3.5 x 10(-3)) in the obese group. However, in an extension study of 1938 subjects from the population-based Hong Kong Cardiovascular Risk Factors Prevalence Study, rs8050136, rs10938397, and rs17782313 showed significant associations with BMI.

Conclusion: We have succeeded in replicating, in a Chinese population, the associations with obesity in seven SNPs reported in recent genome-wide association studies. Further functional and fine-mapping studies to elucidate the roles of these putative obesity-related genes and genetic variants are warranted.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Asian Continental Ancestry Group / genetics
  • Blood Glucose / metabolism
  • Body Mass Index
  • Case-Control Studies
  • Chi-Square Distribution
  • Cross-Sectional Studies
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Genetic Variation
  • Genome-Wide Association Study
  • Glucose Tolerance Test
  • Hong Kong
  • Humans
  • Male
  • Middle Aged
  • Obesity / genetics*
  • Obesity / metabolism
  • Polymorphism, Single Nucleotide / genetics
  • Regression Analysis
  • Risk Factors
  • Waist Circumference

Substances

  • Blood Glucose