FTO Variants Are Associated With Obesity in the Chinese and Malay Populations in Singapore
- Jonathan T. Tan1,
- Rajkumar Dorajoo2,
- Mark Seielstad2,
- Xue Ling Sim1,
- Rick Twee-Hee Ong2,
- Kee Seng Chia1,
- Tien Yin Wong34,
- Seang Mei Saw35,
- Suok Kai Chew6,
- Tin Aung3 and
- E-Shyong Tai17
- 1Center for Molecular Epidemiology, National University of Singapore, Singapore, Singapore
- 2Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore
- 3Singapore Eye Research Institute, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- 4Centre for Eye Research Australia, University of Melbourne, Melbourne, Australia
- 5Department of Community, Occupational and Family Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- 6Ministry of Health, Singapore, Singapore
- 7Department of Endocrinology, Singapore General Hospital, Singapore, Singapore
- Corresponding author: Tai E. Shyong, eshyong{at}pacific.net.sg
Abstract
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.
Footnotes
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Published ahead of print at http://diabetes.diabetesjournals.org on 3 July 2008.
J.T.T. and R.D. contributed equally to this study.
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- Accepted June 19, 2008.
- Received February 15, 2008.
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