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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

Association analysis plots for BMI, waist circumference and percent fat mass in the two study samples of African Americans and West Africans.
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Figure 2: Association analysis plots for BMI, waist circumference and percent fat mass in the two study samples of African Americans and West Africans.

Mentions: Table 2 shows the SNPs displaying P ≤ 0.01 in either study population or in the meta-analysis. The top scoring SNPs for BMI were in intron 8 (Fig 2). For WC and PFM, the most significantly associated SNPs were in intron 8 or intron 1 (Table 2, Fig 2). The effect sizes for BMI were 0.9–1.7 kg/m2 in West Africans, ∼1–1.6 kg/m2 in African Americans, and ∼0.8 kg/m2 in the meta-analysis for the two significant SNPs showing consistent direction of effect. The effect sizes for WC and PFM are shown in Table 2. Some SNPs (one for BMI, one for WC, and three for PFM) showed significant heterogeneity of association between the two study samples (Table 2). Haplotype analysis around these top-scoring SNPs showed that none of the haplotypes had a stronger association with any of the traits than the single SNPs they contained (data not shown). The only nonsynonymous coding SNP, rs16952624 (A405V), in this study (MAF 0.041 in West Africans, 0.024 in African Americans) showed no association with any of the obesity phenotypes in the West African (P 0.52–0.70) or African American sample (P 0.18–0.67). We note that none of the discovery SNPs in intron 8 reached statistical significance at a P value threshold of 0.0002 after correcting for multiple comparisons using the conservative Bonferroni-correction method.


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)

Association analysis plots for BMI, waist circumference and percent fat mass in the two study samples of African Americans and West Africans.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

Figure 2: Association analysis plots for BMI, waist circumference and percent fat mass in the two study samples of African Americans and West Africans.
Mentions: Table 2 shows the SNPs displaying P ≤ 0.01 in either study population or in the meta-analysis. The top scoring SNPs for BMI were in intron 8 (Fig 2). For WC and PFM, the most significantly associated SNPs were in intron 8 or intron 1 (Table 2, Fig 2). The effect sizes for BMI were 0.9–1.7 kg/m2 in West Africans, ∼1–1.6 kg/m2 in African Americans, and ∼0.8 kg/m2 in the meta-analysis for the two significant SNPs showing consistent direction of effect. The effect sizes for WC and PFM are shown in Table 2. Some SNPs (one for BMI, one for WC, and three for PFM) showed significant heterogeneity of association between the two study samples (Table 2). Haplotype analysis around these top-scoring SNPs showed that none of the haplotypes had a stronger association with any of the traits than the single SNPs they contained (data not shown). The only nonsynonymous coding SNP, rs16952624 (A405V), in this study (MAF 0.041 in West Africans, 0.024 in African Americans) showed no association with any of the obesity phenotypes in the West African (P 0.52–0.70) or African American sample (P 0.18–0.67). We note that none of the discovery SNPs in intron 8 reached statistical significance at a P value threshold of 0.0002 after correcting for multiple comparisons using the conservative Bonferroni-correction method.

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