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FTO genetic variation and association with obesity in West Africans and African Americans.

Adeyemo A, Chen G, Zhou J, Shriner D, Doumatey A, Huang H, Rotimi C - Diabetes (2010)

Bottom Line: As expected, both African-ancestry samples showed weaker linkage disequilibrium (LD) patterns compared with other continental (e.g., European) populations.The combined effect size for BMI for the top SNPs from meta-analysis was 0.77 kg/m(2) (P = 0.009, rs9932411) and 0.70 kg/m(2) (P = 0.006, rs7191513).The FTO gene shows significant differences in allele frequency and LD patterns in populations of African ancestry compared with other continental populations.

View Article: PubMed Central - PubMed

Affiliation: Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA. adeyemoa@mail.nih.gov

ABSTRACT

Objective: The FTO gene is one of the most consistently replicated loci for obesity. However, data from populations of African ancestry are limited. We evaluated genetic variation in the FTO gene and investigated associations with obesity in West Africans and African Americans.

Research design and methods: The study samples comprised 968 African Americans (59% female, mean age 49 years, mean BMI 30.8 kg/m(2)) and 517 West Africans (58% female, mean age 54 years, mean BMI 25.5 kg/m(2)). FTO genetic variation was evaluated by genotyping 262 tag single nucleotide polymorphisms (SNPs) across the entire gene. Association of each SNP with BMI, waist circumference, and percent fat mass was investigated under an additive model.

Results: As expected, both African-ancestry samples showed weaker linkage disequilibrium (LD) patterns compared with other continental (e.g., European) populations. Several intron 8 SNPs, in addition to intron 1 SNPs, showed significant associations in both study samples. The combined effect size for BMI for the top SNPs from meta-analysis was 0.77 kg/m(2) (P = 0.009, rs9932411) and 0.70 kg/m(2) (P = 0.006, rs7191513). Two previously reported associations with intron 1 SNPs (rs1121980 and rs7204609, r(2) = 0.001) were replicated among the West Africans.

Conclusions: The FTO gene shows significant differences in allele frequency and LD patterns in populations of African ancestry compared with other continental populations. Despite these differences, we observed evidence of associations with obesity in African Americans and West Africans, as well as evidence of heterogeneity in association. More studies of FTO in multiple ethnic groups are needed.

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Related in: MedlinePlus

LD patterns across the FTO gene in the two study samples (African Americans and West Africans) and in four HapMap population samples (European, CEU; East Asian, CHB and JPT; and African, YRI). (A high-quality digital representation of this figure is available in the online issue.)
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Figure 1: LD patterns across the FTO gene in the two study samples (African Americans and West Africans) and in four HapMap population samples (European, CEU; East Asian, CHB and JPT; and African, YRI). (A high-quality digital representation of this figure is available in the online issue.)

Mentions: The LD structure across the gene in both study samples is shown in Fig. 1. Using the CI method of Gabriel et al. (10) to construct haplotype blocks, the African American sample had 59 haplotype blocks with 138 SNPs outside blocks while the West African sample had 58 blocks with 142 SNPs outside blocks. The LD structure in the two study samples is more fragmented than European or Asian continental populations (represented by the HapMap CEU and JPT/CHB samples, respectively) (Fig. 1 and supplementary Fig. 2). This pattern of low LD was also observed for the intron 1 region surrounding rs9939609, the most consistently reported obesity-associated FTO SNP (supplementary Fig. 3). Using a common set of polymorphic SNPs, the proportion of SNPs exceeding specific r2 thresholds of 0.2, 0.4, 0.6, and 0.8, respectively, in the HapMap CEU, CHB, and JPT samples were approximately threefold higher than those in the present study and the HapMap YRI sample (P < 0.0001, supplementary Fig. 2, and supplementary Table 2). In contrast, there were no significant differences in these proportions between the West African and African American samples in the present study or between these and the HapMap YRI sample.


FTO genetic variation and association with obesity in West Africans and African Americans.

Adeyemo A, Chen G, Zhou J, Shriner D, Doumatey A, Huang H, Rotimi C - Diabetes (2010)

LD patterns across the FTO gene in the two study samples (African Americans and West Africans) and in four HapMap population samples (European, CEU; East Asian, CHB and JPT; and African, YRI). (A high-quality digital representation of this figure is available in the online issue.)
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2874717&req=5

Figure 1: LD patterns across the FTO gene in the two study samples (African Americans and West Africans) and in four HapMap population samples (European, CEU; East Asian, CHB and JPT; and African, YRI). (A high-quality digital representation of this figure is available in the online issue.)
Mentions: The LD structure across the gene in both study samples is shown in Fig. 1. Using the CI method of Gabriel et al. (10) to construct haplotype blocks, the African American sample had 59 haplotype blocks with 138 SNPs outside blocks while the West African sample had 58 blocks with 142 SNPs outside blocks. The LD structure in the two study samples is more fragmented than European or Asian continental populations (represented by the HapMap CEU and JPT/CHB samples, respectively) (Fig. 1 and supplementary Fig. 2). This pattern of low LD was also observed for the intron 1 region surrounding rs9939609, the most consistently reported obesity-associated FTO SNP (supplementary Fig. 3). Using a common set of polymorphic SNPs, the proportion of SNPs exceeding specific r2 thresholds of 0.2, 0.4, 0.6, and 0.8, respectively, in the HapMap CEU, CHB, and JPT samples were approximately threefold higher than those in the present study and the HapMap YRI sample (P < 0.0001, supplementary Fig. 2, and supplementary Table 2). In contrast, there were no significant differences in these proportions between the West African and African American samples in the present study or between these and the HapMap YRI sample.

Bottom Line: As expected, both African-ancestry samples showed weaker linkage disequilibrium (LD) patterns compared with other continental (e.g., European) populations.The combined effect size for BMI for the top SNPs from meta-analysis was 0.77 kg/m(2) (P = 0.009, rs9932411) and 0.70 kg/m(2) (P = 0.006, rs7191513).The FTO gene shows significant differences in allele frequency and LD patterns in populations of African ancestry compared with other continental populations.

View Article: PubMed Central - PubMed

Affiliation: Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA. adeyemoa@mail.nih.gov

ABSTRACT

Objective: The FTO gene is one of the most consistently replicated loci for obesity. However, data from populations of African ancestry are limited. We evaluated genetic variation in the FTO gene and investigated associations with obesity in West Africans and African Americans.

Research design and methods: The study samples comprised 968 African Americans (59% female, mean age 49 years, mean BMI 30.8 kg/m(2)) and 517 West Africans (58% female, mean age 54 years, mean BMI 25.5 kg/m(2)). FTO genetic variation was evaluated by genotyping 262 tag single nucleotide polymorphisms (SNPs) across the entire gene. Association of each SNP with BMI, waist circumference, and percent fat mass was investigated under an additive model.

Results: As expected, both African-ancestry samples showed weaker linkage disequilibrium (LD) patterns compared with other continental (e.g., European) populations. Several intron 8 SNPs, in addition to intron 1 SNPs, showed significant associations in both study samples. The combined effect size for BMI for the top SNPs from meta-analysis was 0.77 kg/m(2) (P = 0.009, rs9932411) and 0.70 kg/m(2) (P = 0.006, rs7191513). Two previously reported associations with intron 1 SNPs (rs1121980 and rs7204609, r(2) = 0.001) were replicated among the West Africans.

Conclusions: The FTO gene shows significant differences in allele frequency and LD patterns in populations of African ancestry compared with other continental populations. Despite these differences, we observed evidence of associations with obesity in African Americans and West Africans, as well as evidence of heterogeneity in association. More studies of FTO in multiple ethnic groups are needed.

Show MeSH
Related in: MedlinePlus