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

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Authors
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
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
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Issue Date
2012

Metadata
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Citation
PLoS ONE 2012, 7(1):e29202
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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Additional Links
http://dx.doi.org/10.1371/journal.pone.0029202
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3251563/
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Archived with thanks to PloS one
ae974a485f413a2113503eed53cd6c53
10.1371/journal.pone.0029202
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