A genome-wide association search for type 2 diabetes genes in African Americans by Palmer Nicholette D, McDonough Caitrin W, Hicks Pamela J, Roh Bong H, Wing Maria R, An S Sandy, Hester Jessica M, Cooke Jessica N, Bostrom Meredith A, Rudock Megan E, Talbert Matthew E, Lewis Joshua P, DIAGRAM Consortium, MAGIC Investigators, Ferrara Assiamira, Lu Lingyi, Ziegler Julie T, Sale Michele M, Divers Jasmin, Shriner Daniel, Adeyemo Adebowale, Rotimi Charles N, Ng Maggie C Y, Langefeld Carl D, Freedman Barry I, Bowden Donald W, Voight Benjamin F, Scott Laura J, Steinthorsdottir Valgerdur, Morris Andrew P, Dina Christian, Welch Ryan P, Zeggini Eleftheria, Huth Cornelia, Aulchenko Yurii S, Thorleifsson Gudmar, McCulloch Laura J, Ferreira Teresa, Grallert Harald, Amin Najaf, Wu Guanming, Willer Cristen J, Raychaudhuri Soumya, McCarroll Steve A, Langenberg Claudia, Hofmann Oliver M, Dupuis Josée, Qi Lu, Segrè Ayellet V, van Hoek Mandy, Navarro Pau, Ardlie Kristin, Balkau Beverley, Benediktsson Rafn, Bennett Amanda J, Blagieva Roza, Boerwinkle Eric, Bonnycastle Lori L, Boström Kristina Bengtsson, Bravenboer Bert, Bumpstead Suzannah, Burtt Noël P, Charpentier Guillaume, Chines Peter S, Cornelis Marilyn, Couper David J, Crawford Gabe, Doney Alex S F, Elliott Katherine S, Elliott Amanda L, Erdos Michael R, Fox Caroline S, Franklin Christopher S, Ganser Martha, Gieger Christian, Grarup Niels, Green Todd, Griffin Simon, Groves Christopher J, Guiducci Candace, Hadjadj Samy, Hassanali Neelam, Herder Christian, Isomaa Bo, Jackson Anne U, Johnson Paul R V, Jørgensen Torben, Kao Wen H L, Klopp Norman, Kong Augustine, Kraft Peter, Kuusisto Johanna, Lauritzen Torsten, Li Man, Lieverse Aloysius, Lindgren Cecilia M, Lyssenko Valeriya, Marre Michel, Meitinger Thomas, Midthjell Kristian, Morken Mario A, Narisu Narisu, Nilsson Peter, Owen Katharine R, Payne Felicity, Perry John R B, Petersen Ann-Kristin, Platou Carl, Proença Christine, Prokopenko Inga, Rathmann Wolfgang, Rayner N William, Robertson Neil R, Rocheleau Ghislain, Roden Michael, Sampson Michael J, Saxena Richa, Shields Beverley M, Shrader Peter, Sigurdsson Gunnar, Sparsø Thomas, Strassburger Klaus, Stringham Heather M, Sun Qi, Swift Amy J, Thorand Barbara, Tichet Jean, Tuomi Tiinamaija, van Dam Rob M, van Haeften Timon W, van Herpt Thijs, van Vliet-Ostaptchouk Jana V, Walters G Bragi, Weedon Michael N, Wijmenga Cisca, Witteman Jacqueline, Bergman Richard N, Cauchi Stephane, Collins Francis S, Gloyn Anna L, Gyllensten Ulf, Hansen Torben, Hide Winston A, Hitman Graham A, Hofman Albert, Hunter David J, Hveem Kristian, Laakso Markku, Mohlke Karen L, Morris Andrew D, Palmer Colin N A, Pramstaller Peter P, Rudan Igor, Sijbrands Eric, Stein Lincoln D, Tuomilehto Jaakko, Uitterlinden Andre, Walker Mark, Wareham Nicholas J, Watanabe Richard M, Abecasis Goncalo R, Boehm Bernhard O, Campbell Harry, Daly Mark J, Hattersley Andrew T, Hu Frank B, Meigs James B, Pankow James S, Pedersen Oluf, Wichmann H-Erich, Barroso Inês, Florez Jose C, Frayling Timothy M, Groop Leif, Sladek Rob, Thorsteinsdottir Unnur, Wilson James F, Illig Thomas, Froguel Philippe, van Duijn Cornelia M, Stefansson Kari, Altshuler David, Boehnke Michael, McCarthy Mark I, Soranzo Nicole, Wheeler Eleanor, Glazer Nicole L, Bouatia-Naji Nabila, Mägi Reedik, Randall Joshua, Johnson Toby, Elliott Paul, Rybin Denis, Henneman Peter, Dehghan Abbas, Hottenga Jouke Jan, Song Kijoung, Goel Anuj, Egan Josephine M, Lajunen Taina, Doney Alex, Kanoni Stavroula, Cavalcanti-Proença Christine, Kumari Meena, Timpson Nicholas J, Zabena Carina, Ingelsson Erik, An Ping, O'Connell Jeffrey, Luan Jian'an, Elliott Amanda, McCarroll Steven A, Roccasecca Rosa Maria, Pattou François, Sethupathy Praveen, Ariyurek Yavuz, Barter Philip, Beilby John P, Ben-Shlomo Yoav, Bergmann Sven, Bochud Murielle, Bonnefond Amélie, Borch-Johnsen Knut, Böttcher Yvonne, Brunner Eric, Bumpstead Suzannah J, Chen Yii-Der Ida, Chines Peter, Clarke Robert, Coin Lachlan J M, Cooper Matthew N, Crisponi Laura, Day Ian N M, de Geus Eco J C, Delplanque Jerome, Fedson Annette C, Fischer-Rosinsky Antje, Forouhi Nita G, Frants Rune, Franzosi Maria Grazia, Galan Pilar, Goodarzi Mark O, Graessler Jürgen, Grundy Scott, Gwilliam Rhian, Hallmans Göran, Hammond Naomi, Han Xijing, Hartikainen Anna-Liisa, Hayward Caroline, Heath Simon C, Hercberg Serge, Hicks Andrew A, Hillman David R, Hingorani Aroon D, Hui Jennie, Hung Joe, Jula Antti, Kaakinen Marika, Kaprio Jaakko, Kesaniemi Y Antero, Kivimaki Mika, Knight Beatrice, Koskinen Seppo, Kovacs Peter, Kyvik Kirsten Ohm, Lathrop G Mark, Lawlor Debbie A, Le Bacquer Olivier, Lecoeur Cécile, Li Yun, Mahley Robert, Mangino Massimo, Manning Alisa K, Martínez-Larrad María Teresa, McAteer Jarred B, McPherson Ruth, Meisinger Christa, Melzer David, Meyre David, Mitchell Braxton D, Mukherjee Sutapa, Naitza Silvia, Neville Matthew J, Oostra Ben A, Orrù Marco, Pakyz Ruth, Paolisso Giuseppe, Pattaro Cristian, Pearson Daniel, Peden John F, Pedersen Nancy L, Perola Markus, Pfeiffer Andreas F H, Pichler Irene, Polasek Ozren, Posthuma Danielle, Potter Simon C, Pouta Anneli, Province Michael A, Psaty Bruce M, Rayner Nigel W, Rice Kenneth, Ripatti Samuli, Rivadeneira Fernando, Rolandsson Olov, Sandbaek Annelli, Sandhu Manjinder, Sanna Serena, Sayer Avan Aihie, Scheet Paul, Seedorf Udo, Sharp Stephen J, Shields Beverley, Sijbrands Eric J G, Silveira Angela, Simpson Laila, Singleton Andrew, Smith Nicholas L, Sovio Ulla, Swift Amy, Syddall Holly, Syvänen Ann-Christine, Tanaka Toshiko, Tönjes Anke, Uitterlinden André G, van Dijk Ko Willems, Varma Dhiraj, Visvikis-Siest Sophie, Vitart Veronique, Vogelzangs Nicole, Waeber Gérard, Wagner Peter J, Walley Andrew, Ward Kim L, Watkins Hugh, Wild Sarah H, Willemsen Gonneke, Witteman Jaqueline C M, Yarnell John W G, Zelenika Diana, Zethelius Björn, Zhai Guangju, Zhao Jing Hua, Zillikens M Carola, Borecki Ingrid B, Loos Ruth J F, Meneton Pierre, Magnusson Patrik K E, Nathan David M, Williams Gordon H, Silander Kaisa, Salomaa Veikko, Smith George Davey, Bornstein Stefan R, Schwarz Peter, Spranger Joachim, Karpe Fredrik, Shuldiner Alan R, Cooper Cyrus, Dedoussis George V, Serrano-Ríos Manuel, Lind Lars, Palmer Lyle J, Franks Paul W, Ebrahim Shah, Marmot Michael, Kao W H Linda, Pramstaller Peter Paul, Wright Alan F, Stumvoll Michael, Hamsten Anders, Buchanan Thomas A, Valle Timo T, Rotter Jerome I, Siscovick David S, Penninx Brenda W J H, Boomsma Dorret I, Deloukas Panos, Spector Timothy D, Ferrucci Luigi, Cao Antonio, Scuteri Angelo, Schlessinger David, Uda Manuela, Ruokonen Aimo, Jarvelin Marjo-Riitta, Waterworth Dawn M, Vollenweider Peter, Peltonen Leena, Mooser Vincent, Sladek Robert in PloS one (2012). PubMed

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.

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