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A Genome-Wide Association Search for Type 2 Diabetes Genes in African Americans

Nicholette D. Palmer,Caitrin W. McDonough,Pamela J. Hicks,Bong H. Roh,Maria R. Wing,Seon-Sook 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,Michèle M. Sale,Jasmin Divers,Daniel Shriner,Adebowale Adeyemo,Charles N. Rotimi,Ng Mcy.,Carl D. Langefeld,Barry I. Freedman,Donald W. Bowden,Ben Voight,Laura J. Scott,Valgerður Steinthórsdóttir,Andrew P. Morris,Christian Dina,Ryan Welch,Eleftheria Zeggini,Cornelia Huth,Yurii S. Aulchenko,Guðmar Þorleifsson,Laura McCulloch,Teresa Ferreira,Harald Grallert,Najaf Amin,Guanming Wu,Cristen J. Willer,Soumya Raychaudhuri,Steven A. McCarroll,Claudia Langenberg,Oliver 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,S. J. Bumpstead,Noisel P. Burtt,G. Charpentier,Peter S. Chines,Marilyn C. Cornelis,David J. Couper,Gabe Crawford,Alex S.F. Doney,Kate Elliott,Amanda Elliott,Michael R. Erdos,Caroline S. Fox,Christopher S. Franklin,Martha Ganser,Christian Gieger,Niels Grarup,T Green,Simon J. Griffin,Christopher J. Groves,Candace Guiducci,Samy Hadjadj,Neelam Hassanali,Christian Herder,Bo Isomaa,Anne Jackson,Johnson Prv.,Torben Jørgensen,Kao Whl.,Norman Klopp,Augustine Kong,Peter Kraft,Johanna Kuusisto,Torsten Lauritzen,M Li,Aloysius G. Lieverse,Cecilia M. Lindgren,Valeriya Lyssenko,Michel Marre,Thomas Meitinger,Kristian Midthjell,Mario A. Morken,N Narisu,Peter M. Nilsson,Katharine R. Owen,Felicity Payne,Perry Jrb.,AK Petersen,Carl G. P. Platou,Christine Proença,Inga Prokopenko,Wolfgang Rathmann,Nigel W. Rayner,Neil Robertson,Ghislain Rocheleau,Michael Roden,Michael J. Sampson,Richa Saxena,Beverley M. Shields,Peter Shrader,Gunnar Sigurðsson,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,J. C. M. Witteman,Richard N. Bergman,Stéphane Cauchi,Francis S. Collins,Anna L. Gloyn,Ulf Gyllensten,Torben Hansen,Winston Hide,G. A. Hitman,Albert Hofman,David J. Hunter,Kristian Hveem,Markku Laakso,Karen L. Mohlke,Andrew D. Morris,Palmer Cna.,Peter P. Pramstaller,Igor Rudan,Eric Sijbrands,Lincoln Stein,Jaakko Tuomilehto,André G. Uitterlinden,Mark Walker,Nicholas J. Wareham,Richard M. Watanabe,Gonçalo R. Abecasis,Bernhard O. Boehm,Harry Campbell,Mark J. Daly,Andrew T. Hattersley,Frank B. Hu,James B. Meigs,James S. Pankow,Oluf Pedersen,Wenwu He,Inês Barroso,José C. Florez,Timothy M. Frayling,Leif Groop,Rob Sladek,U Thorsteinsdottir,James F. Wilson,Thomas Illig,Philippe Froguel,Cornelia M. van Duijn,Kāri Stefánsson,David Altshuler,Michael Boehnke,Mark I. McCarthy,Nicole Soranzo,Eleanor Wheeler,Nicole L. Glazer,Nabila Bouatia-Naji,Reedik Mägi,Joshua C. Randall,Toby Johnson,Paul Elliott,Dennis Rybin,Peter Henneman,Abbas Dehghan,Jouke Jan Hottenga,Kijoung Song,Anuj Goel,Josephine M. Egan,Taina K. Lajunen,Alex S. F. Doney,Stavroula Kanoni,Christine Cavalcanti-Proença,Meena Kumari,Nicholas J. Timpson,Carina Zabena,Erik Ingelsson,Peng An,Jeffrey R. O’Connell,Jia Luan,Amanda Elliott,Rosa Maria Roccasecca,François Pattou,Praveen Sethupathy,Yavuz Ariyürek,Philip J. Barter,John Beilby,Yoav Ben-Shlomo,Sven Bergmann,Murielle Bochud,Amélie Bonnefond,Knut Borch‐Johnsen,Yvonne Böttcher,Eric J. Brunner,S. J. Bumpstead,Y-Di Chen,Peter S. Chines,Robert Clarke,Lachlan Coin,Matthew N. Cooper,Laura Crisponi,Inm Day,Eco J. C. de Geus,Jérôme Delplanque,Annette C. Fedson,Antje Fischer-Rosinský,Nita G. Forouhi,Rune R. Frants,M.G. Franzosi,Pilar Galán,Mark O. Goodarzi,J. Graessler,Scott M. Grundy,Rhian Gwilliam,Göran Hallmans,Naomi Hammond,Xijing Han,Hartikainen Al,Caroline Hayward,Simon Heath,Serge Herçberg,Andrew A. Hicks,David R. Hillman,Aroon D. Hingorani,Jennie Hui,Joe Hung,Antti Jula,Marika Kaakinen,Jaakko Kaprio,Y. Antero Kesäniemi,Mika Kivimäki,Beatrice Knight,Seppo Koskinen,Peter Kovacs,Kirsten Ohm Kyvik,G.M. Lathrop,Debbie A. Lawlor,Olivier Le Bacquer,Cécile Lecœur,Y Li,Robert W. Mahley,Massimo Mangino,Alisa K. Manning,Martínez-Larrad,Jarred B. McAteer,Ruth McPherson,Christa Meisinger,David Melzer,David Meyre,Braxton D. Mitchell,Sutapa Mukherjee,Silvia Naitza,Matt J. Neville,Ben A. Oostra,Marco Orrù,Ruth E. Pakyz,Giuseppe Paolisso,Cristian Pattaro,Daniel S. Pearson,John F. Peden,Nancy L. Pedersen,Markus Perola,Andreas F. H. Pfeiffer,Irene Pichler,Ozren Polašek,Daniëlle Posthuma,Simon Potter,Anneli Pouta,Michael A. Province,Bruce M. Psaty,Kenneth Rice,Samuli Ripatti,Fernando Rivadeneira,Olov Rolandsson,Anelli Sandbaek,Manjinder S. Sandhu,Serena Sanna,Avan A. Sayer,Paul Scheet,Udo Seedorf,Stephen J. Sharp,Beverley M. Shields,Sijbrands Ejg.,Angela Silveira,Laila Simpson,Andrew Singleton,Nicholas L. Smith,Ulla Sovio,Amy J. Swift,Holly Syddall,Syvänen A-C,Toshiko Tanaka,Anke Tönjes,André G. Uitterlinden,Ko Willems van Dijk,Dhiraj Varma,Sophie Visvikis‐Siest,Véronique Vitart,Nicole Vogelzangs,Gérard Waeber,Peter J. Wagner,Andrew Walley,Kim Ward,Hugh Watkins,Sarah H. Wild,Gonneke Willemsen,Witteman Jcm.,Yarnell Jwg.,Diana Zélénika,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,Gabrielle Williams,Kaisa Silander,Veikko Salomaa,George Davey Smith,Bornstein,Peter E. H. Schwarz,Joachim Spranger,Fredrik Karpe,Alan R. Shuldiner,Cyrus Cooper,George Dedoussis,Manuel Serrano-Rı́os,Lars Lind,Lyle J. Palmer,Paul W. Franks,Shah Ebrahim,Michael Marmot,Alan F. Wright,Michael Stümvoll,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 Järvelin,Dawn Waterworth,Péter Vollenweider,Leena Peltonen,Vincent Mooser

Genome-wide association study

Single-nucleotide polymorphism

Genetics

2012

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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“A Genome-Wide Association Search for Type 2 Diabetes Genes in African Americans” is a paper by Nicholette D. Palmer Caitrin W. McDonough Pamela J. Hicks Bong H. Roh Maria R. Wing Seon-Sook 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 Michèle M. Sale Jasmin Divers Daniel Shriner Adebowale Adeyemo Charles N. Rotimi Ng Mcy. Carl D. Langefeld Barry I. Freedman Donald W. Bowden Ben Voight Laura J. Scott Valgerður Steinthórsdóttir Andrew P. Morris Christian Dina Ryan Welch Eleftheria Zeggini Cornelia Huth Yurii S. Aulchenko Guðmar Þorleifsson Laura McCulloch Teresa Ferreira Harald Grallert Najaf Amin Guanming Wu Cristen J. Willer Soumya Raychaudhuri Steven A. McCarroll Claudia Langenberg Oliver 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 S. J. Bumpstead Noisel P. Burtt G. Charpentier Peter S. Chines Marilyn C. Cornelis David J. Couper Gabe Crawford Alex S.F. Doney Kate Elliott Amanda Elliott Michael R. Erdos Caroline S. Fox Christopher S. Franklin Martha Ganser Christian Gieger Niels Grarup T Green Simon J. Griffin Christopher J. Groves Candace Guiducci Samy Hadjadj Neelam Hassanali Christian Herder Bo Isomaa Anne Jackson Johnson Prv. Torben Jørgensen Kao Whl. Norman Klopp Augustine Kong Peter Kraft Johanna Kuusisto Torsten Lauritzen M Li Aloysius G. Lieverse Cecilia M. Lindgren Valeriya Lyssenko Michel Marre Thomas Meitinger Kristian Midthjell Mario A. Morken N Narisu Peter M. Nilsson Katharine R. Owen Felicity Payne Perry Jrb. AK Petersen Carl G. P. Platou Christine Proença Inga Prokopenko Wolfgang Rathmann Nigel W. Rayner Neil Robertson Ghislain Rocheleau Michael Roden Michael J. Sampson Richa Saxena Beverley M. Shields Peter Shrader Gunnar Sigurðsson 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 J. C. M. Witteman Richard N. Bergman Stéphane Cauchi Francis S. Collins Anna L. Gloyn Ulf Gyllensten Torben Hansen Winston Hide G. A. Hitman Albert Hofman David J. Hunter Kristian Hveem Markku Laakso Karen L. Mohlke Andrew D. Morris Palmer Cna. Peter P. Pramstaller Igor Rudan Eric Sijbrands Lincoln Stein Jaakko Tuomilehto André G. Uitterlinden Mark Walker Nicholas J. Wareham Richard M. Watanabe Gonçalo R. Abecasis Bernhard O. Boehm Harry Campbell Mark J. Daly Andrew T. Hattersley Frank B. Hu James B. Meigs James S. Pankow Oluf Pedersen Wenwu He Inês Barroso José C. Florez Timothy M. Frayling Leif Groop Rob Sladek U Thorsteinsdottir James F. Wilson Thomas Illig Philippe Froguel Cornelia M. van Duijn Kāri Stefánsson David Altshuler Michael Boehnke Mark I. McCarthy Nicole Soranzo Eleanor Wheeler Nicole L. Glazer Nabila Bouatia-Naji Reedik Mägi Joshua C. Randall Toby Johnson Paul Elliott Dennis Rybin Peter Henneman Abbas Dehghan Jouke Jan Hottenga Kijoung Song Anuj Goel Josephine M. Egan Taina K. Lajunen Alex S. F. Doney Stavroula Kanoni Christine Cavalcanti-Proença Meena Kumari Nicholas J. Timpson Carina Zabena Erik Ingelsson Peng An Jeffrey R. O’Connell Jia Luan Amanda Elliott Rosa Maria Roccasecca François Pattou Praveen Sethupathy Yavuz Ariyürek Philip J. Barter John Beilby Yoav Ben-Shlomo Sven Bergmann Murielle Bochud Amélie Bonnefond Knut Borch‐Johnsen Yvonne Böttcher Eric J. Brunner S. J. Bumpstead Y-Di Chen Peter S. Chines Robert Clarke Lachlan Coin Matthew N. Cooper Laura Crisponi Inm Day Eco J. C. de Geus Jérôme Delplanque Annette C. Fedson Antje Fischer-Rosinský Nita G. Forouhi Rune R. Frants M.G. Franzosi Pilar Galán Mark O. Goodarzi J. Graessler Scott M. Grundy Rhian Gwilliam Göran Hallmans Naomi Hammond Xijing Han Hartikainen Al Caroline Hayward Simon Heath Serge Herçberg Andrew A. Hicks David R. Hillman Aroon D. Hingorani Jennie Hui Joe Hung Antti Jula Marika Kaakinen Jaakko Kaprio Y. Antero Kesäniemi Mika Kivimäki Beatrice Knight Seppo Koskinen Peter Kovacs Kirsten Ohm Kyvik G.M. Lathrop Debbie A. Lawlor Olivier Le Bacquer Cécile Lecœur Y Li Robert W. Mahley Massimo Mangino Alisa K. Manning Martínez-Larrad Jarred B. McAteer Ruth McPherson Christa Meisinger David Melzer David Meyre Braxton D. Mitchell Sutapa Mukherjee Silvia Naitza Matt J. Neville Ben A. Oostra Marco Orrù Ruth E. Pakyz Giuseppe Paolisso Cristian Pattaro Daniel S. Pearson John F. Peden Nancy L. Pedersen Markus Perola Andreas F. H. Pfeiffer Irene Pichler Ozren Polašek Daniëlle Posthuma Simon Potter Anneli Pouta Michael A. Province Bruce M. Psaty Kenneth Rice Samuli Ripatti Fernando Rivadeneira Olov Rolandsson Anelli Sandbaek Manjinder S. Sandhu Serena Sanna Avan A. Sayer Paul Scheet Udo Seedorf Stephen J. Sharp Beverley M. Shields Sijbrands Ejg. Angela Silveira Laila Simpson Andrew Singleton Nicholas L. Smith Ulla Sovio Amy J. Swift Holly Syddall Syvänen A-C Toshiko Tanaka Anke Tönjes André G. Uitterlinden Ko Willems van Dijk Dhiraj Varma Sophie Visvikis‐Siest Véronique Vitart Nicole Vogelzangs Gérard Waeber Peter J. Wagner Andrew Walley Kim Ward Hugh Watkins Sarah H. Wild Gonneke Willemsen Witteman Jcm. Yarnell Jwg. Diana Zélénika 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 Gabrielle Williams Kaisa Silander Veikko Salomaa George Davey Smith Bornstein Peter E. H. Schwarz Joachim Spranger Fredrik Karpe Alan R. Shuldiner Cyrus Cooper George Dedoussis Manuel Serrano-Rı́os Lars Lind Lyle J. Palmer Paul W. Franks Shah Ebrahim Michael Marmot Alan F. Wright Michael Stümvoll 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 Järvelin Dawn Waterworth Péter Vollenweider Leena Peltonen Vincent Mooser published in 2012. It has an Open Access status of “gold”. You can read and download a PDF Full Text of this paper here.