Obesity Susceptibility Genetic Variants Identified from Recent Genome-Wide Association Studies: Implications in a Chinese Population

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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 ≥27.5 kg/m2) and 700 normal-weight controls (18.5 ≤ BMI ≤ 23.0 kg/m2). 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 × 10−4); FTO rs8050136 (P = 8 × 10−4); MC4R rs17782313 (P = 1.2 × 10−3); KCTD15 rs29941 (P = 8 × 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 × 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 × 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.