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

Palmer, N.D.; McDonough, C.W.; Hicks, P.J.; Roh, B.H.; Wing, M.R.; An, S.S.; Hester, J.M.; Cooke, J.N.; Bostrom, M.A.; Rudock, M.E.; Talbert, M.E.; Lewis, J.P.; Ferrara, A.; Ferrara, A.; Lu, L.; Ziegler, J.T.; Sale, M.M.; Divers, J.; Shriner, D.; Adeyemo, A.; Rotimi, C.N.; Ng, M.C.; Langefeld, C.D.; Freedman, B.I.; Bowden, D.W.; Voight, B.F.; Scott, L.J.; Steinthorsdottir, V.; Morris, A.P.; Dina, C.; Welch, R.P.; Zeggini, E.; Huth, C.; Aulchenko, Y.S.; Thorleifsson, G.; McCulloch, L.J.; Ferreira, T.; Grallert, H.; Amin, N.; Wu, G.; Willer, C.J.; Raychaudhuri, S.; McCarroll, S.A.; Langenberg, C.; Hofmann, O.M.; Dupuis, J.; Qi, L.; Segrè, A.V.; van Hoek, M.; Navarro, P.; Ardlie, K.; Balkau, B.; Benediktsson, R.; Bennett, A.J.; Blagieva, R.; Boerwinkle, E.; Bonnycastle, L.L.; Boström, K.B.; Bravenboer, B.; Bumpstead, S.; Burtt, N.P.; Charpentier, G.; Chines, P.S.; Cornelis, M.; Couper, D.J.; Crawford, G.; Doney, A.S.; Elliott, K.S.; Elliott, A.L.; Erdos, M.R.; Fox, C.S.; Franklin, C.S.; Ganser, M.; Gieger, C.; Grarup, N.; Green, T.; Griffin, S.; Groves, C.J.; Guiducci, C.; Hadjadj, S.; Hassanali, N.; Herder, C.; Isomaa, B.; Jackson, A.U.; Johnson, P.R.; Jørgensen, T.; Kao, W.H.; Klopp, N.; Kong, A.; Kraft, P.; Kuusisto, J.; Lauritzen, T.; Li, M.; Lieverse, A.; Lindgren, C.M.; Lyssenko, V.; Marre, M.; Meitinger, T.; Midthjell, K.; Morken, M.A.; Narisu, N.; Nilsson, P.; Owen, K.R.; Payne, F.; Perry, J.R.; Petersen, A.K.; Platou, C.; Proença, C.; Prokopenko, I.; Rathmann, W.; Rayner, N.W.; Robertson, N.R.; Rocheleau, G.; Roden, M.; Sampson, M.J.; Saxena, R.; Shields, B.M.; Shrader, P.; Sigurdsson, G.; Sparsø, T.; Strassburger, K.; Stringham, H.M.; Sun, Q.; Swift, A.J.; Thorand, B.; Tichet, J.; Tuomi, T.; van Dam, R.M.; van Haeften, T.W.; van Herpt, T.; van Vliet-Ostaptchouk, J.V.; Walters, G.B.; Weedon, M.N.; Wijmenga, C.; Witteman, J.; Bergman, R.N.; Cauchi, S.; Collins, F.S.; Gloyn, A.L.; Gyllensten, U.; Hansen, T.; Hide, W.A.; Hitman, G.A.; Hofman, A.; Hunter, D.J.; Hveem, K.; Laakso, M.; Mohlke, K.L.; Morris, A.D.; Palmer, C.N.; Pramstaller, P.P.; Rudan, I.; Sijbrands, E.; Stein, L.D.; Tuomilehto, J.; Uitterlinden, A.; Walker, M.; Wareham, N.J.; Watanabe, R.M.; Abecasis, G.R.; Boehm, B.O.; Campbell, H.; Daly, M.J.; Hattersley, A.T.; Hu, F.B.; Meigs, J.B.; Pankow, J.S.; Pedersen, O.; Wichmann, H.E.; Barroso, I.; Florez, J.C.; Frayling, T.M.; Groop, L.; Sladek, R.; Thorsteinsdottir, U.; Wilson, J.F.; Illig, T.; Froguel, P.; van Duijn, C.M.; Stefansson, K.; Altshuler, D.; Boehnke, M.; McCarthy, M.I.; Soranzo, N.; Wheeler, E.; Glazer, N.L.; Bouatia-Naji, N.; Mägi, R.; Randall, J.; Johnson, T.; Elliott, P.; Rybin, D.; Henneman, P.; Dehghan, A.; Hottenga, J.J.; Song, K.; Goel, A.; Egan, J.M.; Lajunen, T.; Doney, A.; Kanoni, S.; Cavalcanti-Proença, C.; Kumari, M.; Timpson, N.J.; Zabena, C.; Ingelsson, E.; An, P.; O'Connell, J.; Luan, J.; Elliott, A.; McCarroll, S.A.; Roccasecca, R.M.; Pattou, F.; Sethupathy, P.; Ariyurek, Y.; Barter, P.; Beilby, J.P.; Ben-Shlomo, Y.; Bergmann, S.; Bochud, M.; Bonnefond, A.; Borch-Johnsen, K.; Böttcher, Y.; Brunner, E.; Bumpstead, S.J.; Chen, Y.D.; Chines, P.; Clarke, R.; Coin, L.J.; Cooper, M.N.; Crisponi, L.; Day, I.N.; de Geus, E.J.; Delplanque, J.; Fedson, A.C.; Fischer-Rosinsky, A.; Forouhi, N.G.; Frants, R.; Franzosi, M.G.; Galan, P.; Goodarzi, M.O.; Graessler, J.; Grundy, S.; Gwilliam, R.; Hallmans, G.; Hammond, N.; Han, X.; Hartikainen, A.L.; Hayward, C.; Heath, S.C.; Hercberg, S.; Hicks, A.A.; Hillman, D.R.; Hingorani, A.D.; Hui, J.; Hung, J.; Jula, A.; Kaakinen, M.; Kaprio, J.; Kesaniemi, Y.A.; Kivimaki, M.; Knight, B.; Koskinen, S.; Kovacs, P.; Kyvik, K.O.; Lathrop, G.M.; Lawlor, D.A.; Le Bacquer, O.; Lecoeur, C.; Li, Y.; Mahley, R.; Mangino, M.; Manning, A.K.; Martínez-Larrad, M.T.; McAteer, J.B.; McPherson, R.; Meisinger, C.; Melzer, D.; Meyre, D.; Mitchell, B.D.; Mukherjee, S.; Naitza, S.; Neville, M.J.; Oostra, B.A.; Orrù, M.; Pakyz, R.; Paolisso, G.; Pattaro, C.; Pearson, D.; Peden, J.F.; Pedersen, N.L.; Perola, M.; Pfeiffer, A.F.; Pichler, I.; Polasek, O.; Posthuma, D.; Potter, S.C.; Pouta, A.; Province, M.A.; Psaty, B.M.; Rayner, N.W.; Rice, K.; Ripatti, S.; Rivadeneira, F.; Rolandsson, O.; Sandbaek, A.; Sandhu, M.; Sanna, S.; Sayer, A.A.; Scheet, P.; Seedorf, U.; Sharp, S.J.; Shields, B.; Sijbrands, E.J.; Silveira, A.; Simpson, L.; Singleton, A.; Smith, N.L.; Sovio, U.; Swift, A.; Syddall, H.; Syvänen, A.C.; Tanaka, T.; Tönjes, A.; Uitterlinden, A.G.; van Dijk, K.W.; Varma, D.; Visvikis-Siest, S.; Vitart, V.; Vogelzangs, N.; Waeber, G.; Wagner, P.J.; Walley, A.; Ward, K.L.; Watkins, H.; Wild, S.H.; Willemsen, G.; Witteman, J.C.; Yarnell, J.W.; Zelenika, D.; Zethelius, B.; Zhai, G.; Zhao, J.H.; Zillikens, M.C.; Borecki, I.B.; Loos, R.J.; Meneton, P.; Magnusson, P.K.; Nathan, D.M.; Williams, G.H.; Silander, K.; Salomaa, V.; Smith, G.D.; Bornstein, S.R.; Schwarz, P.; Spranger, J.; Karpe, F.; Shuldiner, A.R.; Cooper, C.; Dedoussis, G.V.; Serrano-Ríos, M.; Lind, L.; Palmer, L.J.; Franks, P.W.; Ebrahim, S.; Marmot, M.; Kao, W.H.; Pramstaller, P.P.; Wright, A.F.; Stumvoll, M.; Hamsten, A.; Buchanan, T.A.; Valle, T.T.; Rotter, J.I.; Siscovick, D.S.; Penninx, B.W.; Boomsma, D.I.; Deloukas, P.; Spector, T.D.; Ferrucci, L.; Cao, A.; Scuteri, A.; Schlessinger, D.; Uda, M.; Ruokonen, A.; Jarvelin, M.R.; Waterworth, D.M.; Vollenweider, P.; Peltonen, L.; Mooser, V.; Sladek, R.

doi:10.1371/journal.pone.0029202

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

Details

Download: BIB_4426B7A3AA93.P001.pdf (306.54 [Ko])
State: Public
Version: author

Serval ID

serval:BIB_4426B7A3AA93

Type

Article: article from journal or magazin.

Collection

Publications

Institution

UNIL/CHUV

Title

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

Journal

Plos One

Author(s)

Palmer N.D., McDonough C.W., Hicks P.J., Roh B.H., Wing M.R., An S.S., Hester J.M., Cooke J.N., Bostrom M.A., Rudock M.E., Talbert M.E., Lewis J.P., Ferrara A., Ferrara A., Lu L., Ziegler J.T., Sale M.M., Divers J., Shriner D., Adeyemo A., Rotimi C.N., Ng M.C., Langefeld C.D., Freedman B.I., Bowden D.W., Voight B.F., Scott L.J., Steinthorsdottir V., Morris A.P., Dina C., Welch R.P., Zeggini E., Huth C., Aulchenko Y.S., Thorleifsson G., McCulloch L.J., Ferreira T., Grallert H., Amin N., Wu G., Willer C.J., Raychaudhuri S., McCarroll S.A., Langenberg C., Hofmann O.M., Dupuis J., Qi L., Segrè A.V., van Hoek M., Navarro P., Ardlie K., Balkau B., Benediktsson R., Bennett A.J., Blagieva R., Boerwinkle E., Bonnycastle L.L., Boström K.B., Bravenboer B., Bumpstead S., Burtt N.P., Charpentier G., Chines P.S., Cornelis M., Couper D.J., Crawford G., Doney A.S., Elliott K.S., Elliott A.L., Erdos M.R., Fox C.S., Franklin C.S., Ganser M., Gieger C., Grarup N., Green T., Griffin S., Groves C.J., Guiducci C., Hadjadj S., Hassanali N., Herder C., Isomaa B., Jackson A.U., Johnson P.R., Jørgensen T., Kao W.H., Klopp N., Kong A., Kraft P., Kuusisto J., Lauritzen T., Li M., Lieverse A., Lindgren C.M., Lyssenko V., Marre M., Meitinger T., Midthjell K., Morken M.A., Narisu N., Nilsson P., Owen K.R., Payne F., Perry J.R., Petersen A.K., Platou C., Proença C., Prokopenko I., Rathmann W., Rayner N.W., Robertson N.R., Rocheleau G., Roden M., Sampson M.J., Saxena R., Shields B.M., Shrader P., Sigurdsson G., Sparsø T., Strassburger K., Stringham H.M., Sun Q., Swift A.J., Thorand B., Tichet J., Tuomi T., van Dam R.M., van Haeften T.W., van Herpt T., van Vliet-Ostaptchouk J.V., Walters G.B., Weedon M.N., Wijmenga C., Witteman J., Bergman R.N., Cauchi S., Collins F.S., Gloyn A.L., Gyllensten U., Hansen T., Hide W.A., Hitman G.A., Hofman A., Hunter D.J., Hveem K., Laakso M., Mohlke K.L., Morris A.D., Palmer C.N., Pramstaller P.P., Rudan I., Sijbrands E., Stein L.D., Tuomilehto J., Uitterlinden A., Walker M., Wareham N.J., Watanabe R.M., Abecasis G.R., Boehm B.O., Campbell H., Daly M.J., Hattersley A.T., Hu F.B., Meigs J.B., Pankow J.S., Pedersen O., Wichmann H.E., Barroso I., Florez J.C., Frayling T.M., Groop L., Sladek R., Thorsteinsdottir U., Wilson J.F., Illig T., Froguel P., van Duijn C.M., Stefansson K., Altshuler D., Boehnke M., McCarthy M.I., Soranzo N., Wheeler E., Glazer N.L., Bouatia-Naji N., Mägi R., Randall J., Johnson T., Elliott P., Rybin D., Henneman P., Dehghan A., Hottenga J.J., Song K., Goel A., Egan J.M., Lajunen T., Doney A., Kanoni S., Cavalcanti-Proença C., Kumari M., Timpson N.J., Zabena C., Ingelsson E., An P., O'Connell J., Luan J., Elliott A., McCarroll S.A., Roccasecca R.M., Pattou F., Sethupathy P., Ariyurek Y., Barter P., Beilby J.P., Ben-Shlomo Y., Bergmann S., Bochud M., Bonnefond A., Borch-Johnsen K., Böttcher Y., Brunner E., Bumpstead S.J., Chen Y.D., Chines P., Clarke R., Coin L.J., Cooper M.N., Crisponi L., Day I.N., de Geus E.J., Delplanque J., Fedson A.C., Fischer-Rosinsky A., Forouhi N.G., Frants R., Franzosi M.G., Galan P., Goodarzi M.O., Graessler J., Grundy S., Gwilliam R., Hallmans G., Hammond N., Han X., Hartikainen A.L., Hayward C., Heath S.C., Hercberg S., Hicks A.A., Hillman D.R., Hingorani A.D., Hui J., Hung J., Jula A., Kaakinen M., Kaprio J., Kesaniemi Y.A., Kivimaki M., Knight B., Koskinen S., Kovacs P., Kyvik K.O., Lathrop G.M., Lawlor D.A., Le Bacquer O., Lecoeur C., Li Y., Mahley R., Mangino M., Manning A.K., Martínez-Larrad M.T., McAteer J.B., McPherson R., Meisinger C., Melzer D., Meyre D., Mitchell B.D., Mukherjee S., Naitza S., Neville M.J., Oostra B.A., Orrù M., Pakyz R., Paolisso G., Pattaro C., Pearson D., Peden J.F., Pedersen N.L., Perola M., Pfeiffer A.F., Pichler I., Polasek O., Posthuma D., Potter S.C., Pouta A., Province M.A., Psaty B.M., Rayner N.W., Rice K., Ripatti S., Rivadeneira F., Rolandsson O., Sandbaek A., Sandhu M., Sanna S., Sayer A.A., Scheet P., Seedorf U., Sharp S.J., Shields B., Sijbrands E.J., Silveira A., Simpson L., Singleton A., Smith N.L., Sovio U., Swift A., Syddall H., Syvänen A.C., Tanaka T., Tönjes A., Uitterlinden A.G., van Dijk K.W., Varma D., Visvikis-Siest S., Vitart V., Vogelzangs N., Waeber G., Wagner P.J., Walley A., Ward K.L., Watkins H., Wild S.H., Willemsen G., Witteman J.C., Yarnell J.W., Zelenika D., Zethelius B., Zhai G., Zhao J.H., Zillikens M.C., Borecki I.B., Loos R.J., Meneton P., Magnusson P.K., Nathan D.M., Williams G.H., Silander K., Salomaa V., Smith G.D., Bornstein S.R., Schwarz P., Spranger J., Karpe F., Shuldiner A.R., Cooper C., Dedoussis G.V., Serrano-Ríos M., Lind L., Palmer L.J., Franks P.W., Ebrahim S., Marmot M., Kao W.H., Pramstaller P.P., Wright A.F., Stumvoll M., Hamsten A., Buchanan T.A., Valle T.T., Rotter J.I., Siscovick D.S., Penninx B.W., Boomsma D.I., Deloukas P., Spector T.D., Ferrucci L., Cao A., Scuteri A., Schlessinger D., Uda M., Ruokonen A., Jarvelin M.R., Waterworth D.M., Vollenweider P., Peltonen L., Mooser V., Sladek R.

Working group(s)

DIAGRAM Consortium, MAGIC Investigators

Contributor(s)

Johnson T., Bergman S., Bochud M., Waeber G., Vollenweider P.

ISSN

1932-6203 (Electronic)

ISSN-L

1932-6203

Publication state

Published

Issued date

2012

Peer-reviewed

Oui

Volume

Number

Pages

e29202

Language

english

Notes

Publication types: Journal Article ; Research Support, N.I.H., Extramural
Publication Status: ppublish

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.

Keywords

Adult, African Americans/genetics, Aged, Case-Control Studies, Cohort Studies, Diabetes Mellitus, Type 2/ethnology, Diabetes Mellitus, Type 2/genetics, 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

URN

urn:nbn:ch:serval-BIB_4426B7A3AA937

OAI-PMH

oai:serval.unil.ch:BIB_4426B7A3AA93

DOI

10.1371/journal.pone.0029202

Pubmed

22238593

Web of science

000301070200019

Open Access

Yes