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A genome-wide association search for type 2 diabetes genes in African Americans.

Publication ,  Journal Article
Palmer, ND; McDonough, CW; Hicks, PJ; Roh, BH; Wing, MR; An, SS; Hester, JM; Cooke, JN; Bostrom, MA; Rudock, ME; Talbert, ME; Lewis, JP ...
Published in: PLoS One
2012

African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.

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Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2012

Volume

7

Issue

1

Start / End Page

e29202

Location

United States

Related Subject Headings

  • Validation Studies as Topic
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Meta-Analysis as Topic
  • Male
  • Humans
  • Genotype
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • General Science & Technology
 

Citation

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Chicago
ICMJE
MLA
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Palmer, N. D., McDonough, C. W., Hicks, P. J., Roh, B. H., Wing, M. R., An, S. S., … Mooser, V. (2012). A genome-wide association search for type 2 diabetes genes in African Americans. PLoS One, 7(1), e29202. https://doi.org/10.1371/journal.pone.0029202
Palmer, Nicholette D., Caitrin W. McDonough, Pamela J. Hicks, Bong H. Roh, Maria R. Wing, S Sandy An, Jessica M. Hester, et al. “A genome-wide association search for type 2 diabetes genes in African Americans.PLoS One 7, no. 1 (2012): e29202. https://doi.org/10.1371/journal.pone.0029202.
Palmer ND, McDonough CW, Hicks PJ, Roh BH, Wing MR, An SS, et al. A genome-wide association search for type 2 diabetes genes in African Americans. PLoS One. 2012;7(1):e29202.
Palmer, Nicholette D., et al. “A genome-wide association search for type 2 diabetes genes in African Americans.PLoS One, vol. 7, no. 1, 2012, p. e29202. Pubmed, doi:10.1371/journal.pone.0029202.
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Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2012

Volume

7

Issue

1

Start / End Page

e29202

Location

United States

Related Subject Headings

  • Validation Studies as Topic
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Meta-Analysis as Topic
  • Male
  • Humans
  • Genotype
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • General Science & Technology