FTO variants are associated with obesity in the Chinese and Malay populations in Singapore

OBJECTIVE— Association between genetic variants at the FTO locus and obesity has been consistently observed in populations of European ancestry and inconsistently in non-Europeans. The aim of this study was to examine the effects of FTO variants on obesity and type 2 diabetes in Southeast Asian populations.RESEARCH DESIGN AND METHODS— We examined associations between nine previously reported FTO single nucleotide polymorphisms (SNPs) with obesity, type 2 diabetes, and related traits in 4,298 participants (2,919 Chinese, 785 Malays, and 594 Asian Indians) from the 1998 Singapore National Health Survey (NHS98) and 2,996 Malays from the Singapore Malay Eye Study (SiMES).RESULTS— All nine SNPs exhibited strong linkage disequilibrium (r² = 0.6–0.99), and minor alleles were associated with obesity in the same direction as previous studies with effect sizes ranging from 0.42 to 0.68 kg/m² (P < 0.0001) in NHS98 Chinese, 0.65 to 0.91 kg/m² (P < 0.02) in NHS98 Malays, and 0.52 to 0.64 kg/m² (P < 0.0001) in SiMES Malays after adjustment for age, sex, smoking, alcohol consumption, and exercise. The variants were also associated with type 2 diabetes, though not after adjustment for BMI (with the exception of the SiMES Malays: odds ratio 1.17–1.22; P ≤ 0.026).CONCLUSIONS— FTO variants common among European populations are associated with obesity in ethnic Chinese and Malays in Singapore. Our data do not support the hypothesis that differences in allele frequency or genetic architecture underlie the lack of association observed in some populations of Asian ancestry. Examination of gene-environment interactions involving variants at this locus may provide further insights into the role of FTO in the pathogenesis of human obesity and diabetes.A recent genome-wide association study for type 2 diabetes using a U.K.-based population revealed a novel locus associated with BMI: the fat mass–and obesity-related gene (FTO) on chromosome 16 (1). The representative single-nucleotide polymorphism (SNP), rs9939609, was confirmed to be associated with elevated BMI after replication in more than 38,000 study participants of European ancestry. Further replication of this association has been observed in several populations of distinctly European ancestry (2–6). However, this association is inconsistent in populations of non-European ancestry. A study in Japanese showed an association between variants at this locus and obesity (7) that was not observed in African Americans (6) or Han Chinese (8). The aims of this study were 1) to determine the associations between previously identified obesity-associated SNPs at the FTO locus with obesity and type 2 diabetes in Chinese, Malays, and Asian-Indians and 2) to examine whether any associations were modulated by exercise.