TY - JOUR
T1 - A Genome-Wide Association Search for Type 2 Diabetes Genes in African Americans
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 - DIAGRAM Consortium
AU - MAGIC Investigators
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
AU - Balkau, Beverley
AU - Benediktsson, Rafn
AU - Bennett, Amanda J.
AU - Blagieva, Roza
AU - Boerwinkle, Eric
AU - Bonnycastle, Lori L.
AU - Boström, Kristina Bengtsson
AU - Bravenboer, Bert
AU - Bumpstead, Suzannah
AU - Burtt, Noël P.
AU - Charpentier, Guillaume
AU - Chines, Peter S.
AU - Cornelis, Marilyn
AU - Couper, David J.
AU - Crawford, Gabe
AU - Doney, Alex S.F.
AU - Elliott, Katherine S.
AU - Elliott, Amanda L.
AU - Erdos, Michael R.
AU - Fox, Caroline S.
AU - Franklin, Christopher S.
AU - Ganser, Martha
AU - Gieger, Christian
AU - Grarup, Niels
AU - Green, Todd
AU - Griffin, Simon
AU - Groves, Christopher J.
AU - Guiducci, Candace
AU - Hadjadj, Samy
AU - Hassanali, Neelam
AU - Herder, Christian
AU - Isomaa, Bo
AU - Jackson, Anne U.
AU - Johnson, Paul R.V.
AU - Jørgensen, Torben
AU - Kao, Wen H.L.
AU - Klopp, Norman
AU - Kong, Augustine
AU - Kraft, Peter
AU - Kuusisto, Johanna
AU - Lauritzen, Torsten
AU - Li, Man
AU - Lieverse, Aloysius
AU - Lindgren, Cecilia M.
AU - Lyssenko, Valeriya
AU - Marre, Michel
AU - Meitinger, Thomas
AU - Mid-Thjell, Kristian
AU - Morken, Mario A.
AU - Narisu, Narisu
AU - Nilsson, Peter
AU - Owen, Katharine R.
AU - Payne, Felicity
AU - Perry, John R.B.
AU - Petersen, Ann Kristin
AU - Platou, Carl
AU - Proença, Christine
AU - Prokopenko, Inga
AU - Rathmann, Wolfgang
AU - Rayner, Nigel William
AU - Robertson, Neil R.
AU - Rocheleau, Ghislain
AU - Roden, Michael
AU - Sampson, Michael J.
AU - Saxena, Richa
AU - Shields, Beverley M.
AU - Shrader, Peter
AU - Sigurdsson, Gunnar
AU - Sparsø, Thomas
AU - Strassburger, Klaus
AU - Stringham, Heather M.
AU - Sun, Qi
AU - Swift, Amy
AU - Thorand, Barbara
AU - Tichet, Jean
AU - Tuomi, Tiinamaija
AU - van Dam, Rob M.
AU - van Haeften, Timon W.
AU - van Herpt, Thijs
AU - van Vliet-Ostaptchouk, Jana V.
AU - Walters, G. Bragi
AU - Weedon, Michael N.
AU - Wijmenga, Cisca
AU - Witteman, Jacqueline
AU - Bergman, Richard N.
AU - Cauchi, Stephane
AU - Collins, Francis S.
AU - Gloyn, Anna L.
AU - Gyllensten, Ulf
AU - Hansen, Torben
AU - Hide, Winston A.
AU - Hitman, Graham A.
AU - Hofman, Albert
AU - Hunter, David J.
AU - Hveem, Kristian
AU - Laakso, Markku
AU - Mohlke, Karen L.
AU - Morris, Andrew D.
AU - Palmer, Colin N.A.
AU - Pramstaller, Peter Paul
AU - Rudan, Igor
AU - Sijbrands, Eric
AU - Stein, Lincoln D.
AU - Tuomilehto, Jaakko
AU - Uitterlinden, André G.
AU - Walker, Mark
AU - Wareham, Nicholas J.
AU - Watanabe, Richard M.
AU - Abecasis, Goncalo R.
AU - Boehm, Bernhard O.
AU - Campbell, Harry
AU - Daly, Mark J.
AU - Hattersley, Andrew T.
AU - Hu, Frank B.
AU - Meigs, James B.
AU - Pankow, James S.
AU - Pedersen, Oluf
AU - Wichmann, H. Erich
AU - Barroso, Inês
AU - Florez, Jose C.
AU - Frayling, Timothy M.
AU - Groop, Leif
AU - Sladek, Robert
AU - Thorsteinsdottir, Unnur
AU - Wilson, James F.
AU - Illig, Thomas
AU - Froguel, Philippe
AU - van Duijn, Cornelia M.
AU - Stefansson, Kari
AU - Altshuler, David
AU - Boehnke, Michael
AU - McCarthy, Mark I.
AU - Soranzo, Nicole
AU - Wheeler, Eleanor
AU - Glazer, Nicole L.
AU - Bouatia-Naji, Nabila
AU - Mägi, Reedik
AU - Randall, Joshua
AU - Johnson, Toby
AU - Elliott, Paul
AU - Rybin, Denis
AU - Thorleifsson, Gudmar
AU - Henneman, Peter
AU - Dehghan, Abbas
AU - Hottenga, Jouke Jan
AU - Song, Kijoung
AU - Goel, Anuj
AU - Egan, Josephine M.
AU - Lajunen, Taina
AU - Doney, Alex
AU - Kanoni, Stavroula
AU - Cavalcanti-Proença, Christine
AU - Kumari, Meena
AU - Timpson, Nicholas J.
AU - Zabena, Carina
AU - Ingelsson, Erik
AU - An, Ping
AU - O’connell, Jeffrey
AU - Luan, Jian’An
AU - Roccasecca, Rosa Maria
AU - Pattou, François
AU - Sethupathy, Praveen
AU - Ariyurek, Yavuz
AU - Barter, Philip
AU - Beilby, John P.
AU - Ben-Shlomo, Yoav
AU - Bergmann, Sven
AU - Bochud, Murielle
AU - Bonnefond, Amélie
AU - Borch-Johnsen, Knut
AU - Böttcher, Yvonne
AU - Brunner, Eric
AU - Bumpstead, Suzannah J.
AU - Chen, Yii Der Ida
AU - Chines, Peter
AU - Clarke, Robert
AU - Coin, Lachlan J.M.
AU - Cooper, Matthew N.
AU - Crisponi, Laura
AU - Day, Ian N.M.
AU - Geus, Eco J.Cde
AU - Delplanque, Jerome
AU - Fedson, Annette C.
AU - Fischer-Rosinsky, Antje
AU - Forouhi, Nita G.
AU - Frants, Rune
AU - Franzosi, Maria Grazia
AU - Galan, Pilar
AU - Ogoodarzi, Mark
AU - Graessler, Jürgen
AU - Grundy, Scott
AU - Gwilliam, Rhian
AU - Hallmans, Göran
AU - Hammond, Naomi
AU - Han, Xijing
AU - Hartikainen, Anna Liisa
AU - Hayward, Caroline
AU - Heath, Simon C.
AU - Hercberg, Serge
AU - Mukherjee, Sutapa
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.
UR - http://www.scopus.com/inward/record.url?scp=84855405312&partnerID=8YFLogxK
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 -