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

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Title: A genome-wide association search for type 2 diabetes genes in African Americans.
Authors: Palmer, ND
McDonough, CW
Hicks, PJ
Roh, BH
Wing, MR
An, SS
Hester, JM
Cooke, JN
Bostrom, MA
Rudock, ME
Talbert, ME
Lewis, JP
DIAGRAM Consortium
MAGIC Investigators
Ferrara, A
Lu, L
Ziegler, JT
Sale, MM
Divers, J
Shriner, D
Adeyemo, A
Rotimi, CN
Ng, MC
Langefeld, CD
Freedman, BI
Bowden, DW
Voight, BF
Scott, LJ
Steinthorsdottir, V
Morris, AP
Dina, C
Welch, RP
Zeggini, E
Huth, C
Aulchenko, YS
Thorleifsson, G
McCulloch, LJ
Ferreira, T
Grallert, H
Amin, N
Wu, G
Willer, CJ
Raychaudhuri, S
McCarroll, SA
Langenberg, C
Hofmann, OM
Dupuis, J
Qi, L
Segrè, AV
Van Hoek, M
Navarro, P
Ardlie, K
Balkau, B
Benediktsson, R
Bennett, AJ
Blagieva, R
Boerwinkle, E
Bonnycastle, LL
Boström, KB
Bravenboer, B
Bumpstead, S
Burtt, NP
Charpentier, G
Chines, PS
Cornelis, M
Couper, DJ
Crawford, G
Doney, AS
Elliott, KS
Elliott, AL
Erdos, MR
Fox, CS
Franklin, CS
Ganser, M
Gieger, C
Grarup, N
Green, T
Griffin, S
Groves, CJ
Guiducci, C
Hadjadj, S
Hassanali, N
Herder, C
Isomaa, B
Jackson, AU
Johnson, PR
Jørgensen, T
Kao, WH
Klopp, N
Kong, A
Kraft, P
Kuusisto, J
Lauritzen, T
Li, M
Lieverse, A
Lindgren, CM
Lyssenko, V
Marre, M
Meitinger, T
Midthjell, K
Morken, MA
Narisu, N
Nilsson, P
Owen, KR
Payne, F
Perry, JR
Petersen, AK
Platou, C
Proença, C
Prokopenko, I
Rathmann, W
Rayner, NW
Robertson, NR
Rocheleau, G
Roden, M
Sampson, MJ
Saxena, R
Shields, BM
Shrader, P
Sigurdsson, G
Sparsø, T
Strassburger, K
Stringham, HM
Sun, Q
Swift, AJ
Thorand, B
Tichet, J
Tuomi, T
Van Dam, RM
Van Haeften, TW
Van Herpt, T
Van Vliet-Ostaptchouk, JV
Walters, GB
Weedon, MN
Wijmenga, C
Witteman, J
Bergman, RN
Cauchi, S
Collins, FS
Gloyn, AL
Gyllensten, U
Hansen, T
Hide, WA
Hitman, GA
Hofman, A
Hunter, DJ
Hveem, K
Laakso, M
Mohlke, KL
Morris, AD
Palmer, CN
Pramstaller, PP
Rudan, I
Sijbrands, E
Stein, LD
Tuomilehto, J
Uitterlinden, A
Walker, M
Wareham, NJ
Watanabe, RM
Abecasis, GR
Boehm, BO
Campbell, H
Daly, MJ
Hattersley, AT
Hu, FB
Meigs, JB
Pankow, JS
Pedersen, O
Wichmann, HE
Barroso, I
Florez, JC
Frayling, TM
Groop, L
Sladek, R
Thorsteinsdottir, U
Wilson, JF
Illig, T
Froguel, P
Van Duijn, CM
Stefansson, K
Altshuler, D
Boehnke, M
McCarthy, MI
Soranzo, N
Wheeler, E
Glazer, NL
Bouatia-Naji, N
Mägi, R
Randall, J
Johnson, T
Elliott, P
Rybin, D
Henneman, P
Dehghan, A
Hottenga, JJ
Song, K
Goel, A
Egan, JM
Lajunen, T
Doney, A
Kanoni, S
Cavalcanti-Proença, C
Kumari, M
Timpson, NJ
Zabena, C
Ingelsson, E
An, P
O'Connell, J
Luan, J
Elliott, A
McCarroll, SA
Roccasecca, RM
Pattou, F
Sethupathy, P
Ariyurek, Y
Barter, P
Beilby, JP
Ben-Shlomo, Y
Bergmann, S
Bochud, M
Bonnefond, A
Borch-Johnsen, K
Böttcher, Y
Brunner, E
Bumpstead, SJ
Chen, YD
Chines, P
Clarke, R
Coin, LJ
Cooper, MN
Crisponi, L
Day, IN
De Geus, EJ
Delplanque, J
Fedson, AC
Fischer-Rosinsky, A
Forouhi, NG
Frants, R
Franzosi, MG
Galan, P
Goodarzi, MO
Graessler, J
Grundy, S
Gwilliam, R
Hallmans, G
Hammond, N
Han, X
Hartikainen, AL
Hayward, C
Heath, SC
Hercberg, S
Hicks, AA
Hillman, DR
Hingorani, AD
Hui, J
Hung, J
Jula, A
Kaakinen, M
Kaprio, J
Kesaniemi, YA
Kivimaki, M
Knight, B
Koskinen, S
Kovacs, P
Kyvik, KO
Lathrop, GM
Lawlor, DA
Le Bacquer, O
Lecoeur, C
Li, Y
Mahley, R
Mangino, M
Manning, AK
Martínez-Larrad, MT
McAteer, JB
McPherson, R
Meisinger, C
Melzer, D
Meyre, D
Mitchell, BD
Mukherjee, S
Naitza, S
Neville, MJ
Oostra, BA
Orrù, M
Pakyz, R
Paolisso, G
Pattaro, C
Pearson, D
Peden, JF
Pedersen, NL
Perola, M
Pfeiffer, AF
Pichler, I
Polasek, O
Posthuma, D
Potter, SC
Pouta, A
Province, MA
Psaty, BM
Rayner, NW
Rice, K
Ripatti, S
Rivadeneira, F
Rolandsson, O
Sandbaek, A
Sandhu, M
Sanna, S
Sayer, AA
Scheet, P
Seedorf, U
Sharp, SJ
Shields, B
Sijbrands, EJ
Silveira, A
Simpson, L
Singleton, A
Smith, NL
Sovio, U
Swift, A
Syddall, H
Syvänen, AC
Tanaka, T
Tönjes, A
Uitterlinden, AG
Van Dijk, KW
Varma, D
Visvikis-Siest, S
Vitart, V
Vogelzangs, N
Waeber, G
Wagner, PJ
Walley, A
Ward, KL
Watkins, H
Wild, SH
Willemsen, G
Witteman, JC
Yarnell, JW
Zelenika, D
Zethelius, B
Zhai, G
Zhao, JH
Zillikens, MC
Borecki, IB
Loos, RJ
Meneton, P
Magnusson, PK
Nathan, DM
Williams, GH
Silander, K
Salomaa, V
Smith, GD
Bornstein, SR
Schwarz, P
Spranger, J
Karpe, F
Shuldiner, AR
Cooper, C
Dedoussis, GV
Serrano-Ríos, M
Lind, L
Palmer, LJ
Franks, PW
Ebrahim, S
Marmot, M
Kao, WH
Pramstaller, PP
Wright, AF
Stumvoll, M
Hamsten, A
Buchanan, TA
Valle, TT
Rotter, JI
Siscovick, DS
Penninx, BW
Boomsma, DI
Deloukas, P
Spector, TD
Ferrucci, L
Cao, A
Scuteri, A
Schlessinger, D
Uda, M
Ruokonen, A
Jarvelin, MR
Waterworth, DM
Vollenweider, P
Peltonen, L
Mooser, V
Sladek, R
Item Type: Journal Article
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.
Issue Date: 4-Jan-2012
Date of Acceptance: 22-Nov-2011
URI: http://hdl.handle.net/10044/1/28917
DOI: https://dx.doi.org/10.1371/journal.pone.0029202
ISSN: 1932-6203
Publisher: Public Library of Science
Journal / Book Title: PLOS One
Volume: 7
Issue: 1
Copyright Statement: This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
Sponsor/Funder: Medical Research Council (MRC)
Medical Research Council (MRC)
Funder's Grant Number: G0801056B
G0801056/1
Keywords: Adult
African Americans
Aged
Case-Control Studies
Cohort Studies
Diabetes Mellitus, Type 2
Female
Genetic Predisposition to Disease
Genome-Wide Association Study
Genotype
Humans
Male
Meta-Analysis as Topic
Middle Aged
Polymorphism, Single Nucleotide
Validation Studies as Topic
DIAGRAM Consortium
MAGIC Investigators
General Science & Technology
MD Multidisciplinary
Publication Status: Published
Article Number: e29202
Appears in Collections:National Heart and Lung Institute



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