A genome-wide association search for type 2 diabetes genes in African Americans.
dc.contributor.author | Palmer, Nicholette D | |
dc.contributor.author | McDonough, Caitrin W | |
dc.contributor.author | Hicks, Pamela J | |
dc.contributor.author | Roh, Bong H | |
dc.contributor.author | Wing, Maria R | |
dc.contributor.author | An, S Sandy | |
dc.contributor.author | Hester, Jessica M | |
dc.contributor.author | Cooke, Jessica N | |
dc.contributor.author | Bostrom, Meredith A | |
dc.contributor.author | Rudock, Megan E | |
dc.contributor.author | Talbert, Matthew E | |
dc.contributor.author | Lewis, Joshua P | |
dc.contributor.author | Ferrara, Assiamira | |
dc.contributor.author | Lu, Lingyi | |
dc.contributor.author | Ziegler, Julie T | |
dc.contributor.author | Sale, Michele M | |
dc.contributor.author | Divers, Jasmin | |
dc.contributor.author | Shriner, Daniel | |
dc.contributor.author | Adeyemo, Adebowale | |
dc.contributor.author | Rotimi, Charles N | |
dc.contributor.author | Ng, Maggie C Y | |
dc.contributor.author | Langefeld, Carl D | |
dc.contributor.author | Freedman, Barry I | |
dc.contributor.author | Bowden, Donald W | |
dc.contributor.author | Voight, Benjamin F | |
dc.contributor.author | Scott, Laura J | |
dc.contributor.author | Steinthorsdottir, Valgerdur | |
dc.contributor.author | Morris, Andrew P | |
dc.contributor.author | Dina, Christian | |
dc.contributor.author | Welch, Ryan P | |
dc.contributor.author | Zeggini, Eleftheria | |
dc.contributor.author | Huth, Cornelia | |
dc.contributor.author | Aulchenko, Yurii S | |
dc.contributor.author | Thorleifsson, Gudmar | |
dc.contributor.author | McCulloch, Laura J | |
dc.contributor.author | Ferreira, Teresa | |
dc.contributor.author | Grallert, Harald | |
dc.contributor.author | Amin, Najaf | |
dc.contributor.author | Wu, Guanming | |
dc.contributor.author | Willer, Cristen J | |
dc.contributor.author | Raychaudhuri, Soumya | |
dc.contributor.author | McCarroll, Steve A | |
dc.contributor.author | Langenberg, Claudia | |
dc.contributor.author | Hofmann, Oliver M | |
dc.contributor.author | Dupuis, Josée | |
dc.contributor.author | Qi, Lu | |
dc.contributor.author | Segrè, Ayellet V | |
dc.contributor.author | van Hoek, Mandy | |
dc.contributor.author | Navarro, Pau | |
dc.contributor.author | Ardlie, Kristin | |
dc.contributor.author | Balkau, Beverley | |
dc.contributor.author | Benediktsson, Rafn | |
dc.contributor.author | Bennett, Amanda J | |
dc.contributor.author | Blagieva, Roza | |
dc.contributor.author | Boerwinkle, Eric | |
dc.contributor.author | Bonnycastle, Lori L | |
dc.contributor.author | Boström, Kristina Bengtsson | |
dc.contributor.author | Bravenboer, Bert | |
dc.contributor.author | Bumpstead, Suzannah | |
dc.contributor.author | Burtt, Noël P | |
dc.contributor.author | Charpentier, Guillaume | |
dc.contributor.author | Chines, Peter S | |
dc.contributor.author | Cornelis, Marilyn | |
dc.contributor.author | Couper, David J | |
dc.contributor.author | Crawford, Gabe | |
dc.contributor.author | Doney, Alex S F | |
dc.contributor.author | Elliott, Katherine S | |
dc.contributor.author | Elliott, Amanda L | |
dc.contributor.author | Erdos, Michael R | |
dc.contributor.author | Fox, Caroline S | |
dc.contributor.author | Franklin, Christopher S | |
dc.contributor.author | Ganser, Martha | |
dc.contributor.author | Gieger, Christian | |
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dc.contributor.author | Green, Todd | |
dc.contributor.author | Griffin, Simon | |
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dc.contributor.author | Hassanali, Neelam | |
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dc.contributor.author | Isomaa, Bo | |
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dc.date.accessioned | 2013-09-03T10:55:45Z | |
dc.date.available | 2013-09-03T10:55:45Z | |
dc.date.issued | 2012 | |
dc.identifier.citation | PLoS ONE 2012, 7(1):e29202 | en_GB |
dc.identifier.issn | 1932-6203 | |
dc.identifier.pmid | 22238593 | |
dc.identifier.doi | 10.1371/journal.pone.0029202 | |
dc.identifier.uri | http://hdl.handle.net/2336/300672 | |
dc.description | To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field. | en_GB |
dc.description.abstract | 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. | |
dc.description.sponsorship | National Institutes of Health HHSC268200782096C K99 DK081350 R01 DK066358 R01 DK053591 R01 HL56266 R01 DK070941 Wake Forest University School of Medicine M01 RR07122 | en_GB |
dc.language.iso | en | en |
dc.relation.url | http://dx.doi.org/10.1371/journal.pone.0029202 | en_GB |
dc.relation.url | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3251563/ | en_GB |
dc.rights | Archived with thanks to PloS one | en_GB |
dc.subject.mesh | Adult | en_GB |
dc.subject.mesh | African Americans | en_GB |
dc.subject.mesh | Aged | en_GB |
dc.subject.mesh | Case-Control Studies | en_GB |
dc.subject.mesh | Cohort Studies | en_GB |
dc.subject.mesh | Diabetes Mellitus, Type 2 | en_GB |
dc.subject.mesh | Female | en_GB |
dc.subject.mesh | Genetic Predisposition to Disease | en_GB |
dc.subject.mesh | Genome-Wide Association Study | en_GB |
dc.subject.mesh | Genotype | en_GB |
dc.subject.mesh | Humans | en_GB |
dc.subject.mesh | Male | en_GB |
dc.subject.mesh | Meta-Analysis as Topic | en_GB |
dc.subject.mesh | Middle Aged | en_GB |
dc.subject.mesh | Polymorphism, Single Nucleotide | en_GB |
dc.subject.mesh | Validation Studies as Topic | en_GB |
dc.title | A genome-wide association search for type 2 diabetes genes in African Americans. | en |
dc.type | Article | en |
dc.contributor.department | Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States of America. nallred@wfubmc.edu | en_GB |
dc.identifier.journal | PloS one | en_GB |
dc.rights.access | Open Access - Opinn aðgangur | en |
html.description.abstract | 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. |