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

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dc.contributor.authorPalmer, N.
dc.contributor.authorMcDonough, C.
dc.contributor.authorHicks, P.
dc.contributor.authorRoh, B.
dc.contributor.authorWing, M.
dc.contributor.authorSandy An, S.
dc.contributor.authorHester, J.
dc.contributor.authorCooke, J.
dc.contributor.authorBostrom, M.
dc.contributor.authorRudock, M.
dc.contributor.authorTalbert, M.
dc.contributor.authorLewis, J.
dc.contributor.authorDIAGRAM Consortium,
dc.contributor.authorMAGIC Consortium,
dc.contributor.authorFerrara, A.
dc.contributor.authorLu, L.
dc.contributor.authorZiegler, J.
dc.contributor.authorSale, M.
dc.contributor.authorDivers, J.
dc.contributor.authorShriner, D.
dc.contributor.authoret al.
dc.contributor.editorKronenberg, F.
dc.date.issued2012
dc.description.abstractAfrican 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,2.561028). SNP rs7560163 (P=7.061029, 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,2.561025) 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.
dc.description.statementofresponsibilityNicholette D. Palmer ... DIAGRAM Consortium, MAGIC Investigators ... et al.
dc.identifier.citationPLoS One, 2012; 7(1):e29202-1-e29202-14
dc.identifier.doi10.1371/journal.pone.0029202
dc.identifier.issn1932-6203
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/2440/88580
dc.language.isoen
dc.publisherPublic Library of Science
dc.rightsThis is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
dc.source.urihttps://doi.org/10.1371/journal.pone.0029202
dc.subjectDIAGRAM Consortium
dc.subjectMAGIC Investigators
dc.subjectHumans
dc.subjectDiabetes Mellitus, Type 2
dc.subjectGenetic Predisposition to Disease
dc.subjectCase-Control Studies
dc.subjectCohort Studies
dc.subjectGenotype
dc.subjectPolymorphism, Single Nucleotide
dc.subjectAdult
dc.subjectAged
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectMeta-Analysis as Topic
dc.subjectValidation Studies as Topic
dc.subjectGenome-Wide Association Study
dc.subjectBlack or African American
dc.titleA genome-wide association search for type 2 diabetes genes in African Americans
dc.typeJournal article
pubs.publication-statusPublished

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