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

Tan JT, Dorajoo R, Seielstad M, Sim XL, Ong RT, Chia KS, Wong TY, Saw SM, Chew SK, Aung T, Tai ES - Diabetes (2008)

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Center for Molecular Epidemiology, National University of Singapore, Singapore, Singapore.

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 (r(2) = 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/m(2) (P < 0.0001) in NHS98 Chinese, 0.65 to 0.91 kg/m(2) (P < 0.02) in NHS98 Malays, and 0.52 to 0.64 kg/m(2) (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

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.

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Linkage disequilibrium (r2) between the nine FTO SNPs in the NHS98 and SiMES populations.
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f1: Linkage disequilibrium (r2) between the nine FTO SNPs in the NHS98 and SiMES populations.

Mentions: Table 1 shows the clinical characteristics of the two study populations. Allele frequencies for the nine genotyped SNPs and test for HWE deviation are listed in online appendix Table 1. The MAFs for all nine SNPs were higher in Asian Indians (0.33–0.43) than in Malays (0.28–0.33) or Chinese (0.12–0.18). None of the SNPs showed significant deviation from HWE. Figure 1 illustrates the linkage disequilibrium between the nine FTO SNPs in the different ethnic populations. A high degree of linkage disequilibrium was observed between the SNPs, with similar patterns in all three ethnic groups in our population. In addition, the linkage disequilibrium structure of our population showed similarity to that of the European population (CEU population of HapMap [online appendix Fig. 1]).


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

Tan JT, Dorajoo R, Seielstad M, Sim XL, Ong RT, Chia KS, Wong TY, Saw SM, Chew SK, Aung T, Tai ES - Diabetes (2008)

Linkage disequilibrium (r2) between the nine FTO SNPs in the NHS98 and SiMES populations.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2551698&req=5

f1: Linkage disequilibrium (r2) between the nine FTO SNPs in the NHS98 and SiMES populations.
Mentions: Table 1 shows the clinical characteristics of the two study populations. Allele frequencies for the nine genotyped SNPs and test for HWE deviation are listed in online appendix Table 1. The MAFs for all nine SNPs were higher in Asian Indians (0.33–0.43) than in Malays (0.28–0.33) or Chinese (0.12–0.18). None of the SNPs showed significant deviation from HWE. Figure 1 illustrates the linkage disequilibrium between the nine FTO SNPs in the different ethnic populations. A high degree of linkage disequilibrium was observed between the SNPs, with similar patterns in all three ethnic groups in our population. In addition, the linkage disequilibrium structure of our population showed similarity to that of the European population (CEU population of HapMap [online appendix Fig. 1]).

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Center for Molecular Epidemiology, National University of Singapore, Singapore, Singapore.

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 (r(2) = 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/m(2) (P < 0.0001) in NHS98 Chinese, 0.65 to 0.91 kg/m(2) (P < 0.02) in NHS98 Malays, and 0.52 to 0.64 kg/m(2) (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

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.

Show MeSH
Related in: MedlinePlus