Dataset Information

Genetics of obesity and type 2 diabetes in African Americans.

ABSTRACT: Obesity and type 2 diabetes are highly prevalent and lead to significant morbidity and mortality. In the United States, the impact of these conditions may be worse on historically underserved minorities, particularly African Americans. Genetic ancestry and differences in physiology are unlikely to be the sole or primary determinants of these disparities. In addition, research in this area has the ethically problematic possibility of conflating race with biology. Despite these important considerations and the challenges of conducting this work, population-based approaches for investigating the etiology of obesity and T2D may yield useful information about the pathophysiology of disease, and have implications that extend to all affected individuals. The purpose of this paper is to describe what is understood about the genetic variation that underlies obesity and T2D in African Americans and other individuals of more recent African descent and to highlight several examples that illustrate how ensuring adequate minority representation in genetic research improves its quality. For a variety of reasons a number of unique insights have been possible as a result of these efforts.

SUBMITTER: McCormack S

PROVIDER: S-EPMC3614120 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Genetics of obesity and type 2 diabetes in African Americans.

McCormack Shana S Grant Struan F A SF

Journal of obesity 20130319

Obesity and type 2 diabetes are highly prevalent and lead to significant morbidity and mortality. In the United States, the impact of these conditions may be worse on historically underserved minorities, particularly African Americans. Genetic ancestry and differences in physiology are unlikely to be the sole or primary determinants of these disparities. In addition, research in this area has the ethically problematic possibility of conflating race with biology. Despite these important considera ...[more]

PMID: 23577239

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Project description:The prevalence of type 2 diabetes (T2D) is greater in populations of African descent compared to European-descent populations. Genetic risk factors may underlie the disparity in disease prevalence. Genome-wide association studies (GWAS) have identified >60 common genetic variants that contribute to T2D risk in populations of European, Asian, African and Hispanic descent. These studies have not comprehensively examined population differences in cumulative risk allele load. To investigate the relationship between risk allele load and T2D risk, 46 T2D single nucleotide polymorphisms (SNPs) in 43 loci from GWAS in European, Asian, and African-derived populations were genotyped in 1,990 African Americans (n = 963 T2D cases, n = 1,027 controls) and 1,644 European Americans (n = 719 T2D cases, n = 925 controls) ascertained and recruited using a common protocol in the southeast United States. A genetic risk score (GRS) was constructed from the cumulative risk alleles for each individual. In African American subjects, risk allele frequencies ranged from 0.024 to 0.964. Risk alleles from 26 SNPs demonstrated directional consistency with previous studies, and 3 SNPs from ADAMTS9, TCF7L2, and ZFAND6 showed nominal evidence of association (p < 0.05). African American individuals carried 38-67 (53.7 ± 4.0, mean ± SD) risk alleles. In European American subjects, risk allele frequencies ranged from 0.084 to 0.996. Risk alleles from 36 SNPs demonstrated directional consistency, and 10 SNPs from BCL11A, PSMD6, ADAMTS9, ZFAND3, ANK1, CDKN2A/B, TCF7L2, PRC1, FTO, and BCAR1 showed evidence of association (p < 0.05). European American individuals carried 38-65 (50.9 ± 4.4) risk alleles. African Americans have a significantly greater burden of 2.8 risk alleles (p = 3.97 × 10(-89)) compared to European Americans. However, GRS modeling showed that cumulative risk allele load was associated with risk of T2D in European Americans, but only marginally in African Americans. This result suggests that there are ethnic-specific differences in genetic architecture underlying T2D, and that these differences complicate our understanding of how risk allele load impacts disease susceptibility.

Dataset Information

Genetics of obesity and type 2 diabetes in African Americans.

Publications

Genetics of obesity and type 2 diabetes in African Americans.

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