TY - JOUR
T1 - A genome-wide association search for type 2 diabetes genes in african americans
AU - DIAGRAM Consortium
AU - MAGIC Investigators
AU - Anders Hamsten on behalf of Procardis Consortium
AU - DIAGRAM Consortium
AU - GIANT Consortium
AU - Global BPgen Consortium
AU - for the MAGIC investigators
AU - Palmer, Nicholette D.
AU - McDonough, Caitrin W.
AU - Hicks, Pamela J.
AU - Roh, Bong H.
AU - Wing, Maria R.
AU - An, S. Sandy
AU - Hester, Jessica M.
AU - Cooke, Jessica N.
AU - Bostrom, Meredith A.
AU - Rudock, Megan E.
AU - Talbert, Matthew E.
AU - Lewis, Joshua P.
AU - Ferrara, Assiamira
AU - Lu, Lingyi
AU - Ziegler, Julie T.
AU - Sale, Michele M.
AU - Divers, Jasmin
AU - Shriner, Daniel
AU - Adeyemo, Adebowale
AU - Rotimi, Charles N.
AU - Ng, Maggie C.Y.
AU - Langefeld, Carl D.
AU - Freedman, Barry I.
AU - Bowden, Donald W.
AU - Voight, Benjamin F.
AU - Scott, Laura J.
AU - Steinthorsdottir, Valgerdur
AU - Morris, Andrew P.
AU - Dina, Christian
AU - Welch, Ryan P.
AU - Zeggini, Eleftheria
AU - Huth, Cornelia
AU - Aulchenko, Yurii S.
AU - Thorleifs-Son, Gudmar
AU - McCulloch, Laura J.
AU - Ferreira, Teresa
AU - Grallert, Harald
AU - Amin, Najaf
AU - Wu, Guanming
AU - Willer, Cristen J.
AU - Raychaudhuri, Soumya
AU - McCarroll, Steven A.
AU - Langenberg, Claudia
AU - Hofmann, Oliver M.
AU - Dupuis, Josée
AU - Qi, Lu
AU - Segrè, Ayellet V.
AU - van Hoek, Mandy
AU - Navarro, Pau
AU - Ardlie, Kristin
PY - 2012/1/4
Y1 - 2012/1/4
N2 - 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.
AB - 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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U2 - 10.1371/journal.pone.0029202
DO - 10.1371/journal.pone.0029202
M3 - Article
C2 - 22238593
AN - SCOPUS:84855405312
SN - 1932-6203
VL - 7
JO - PloS one
JF - PloS one
IS - 1
M1 - e29202
ER -