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

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

PLoS One 2012 4;7(1):e29202. Epub 2012 Jan 4.

Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States of America.

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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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3251563PMC
May 2012
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References

(Supplied by CrossRef)
Type 2 diabetes: new genes, new understanding.
I Prokopenko et al.
Trends Genet 2008

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