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Nat Genet. 2014 Sep;46(9):989-93. doi: 10.1038/ng.3043. Epub 2014 Jul 27.

Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease.

Collaborators (471)

Nalls MA, Plagnol V, Hernandez DG, Sharma M, Sheerin UM, Saad M, Simón-Sánchez J, Schulte C, Lesage S, Sveinbjörnsdóttir S, Arepalli S, Barker R, Ben-Shlomo Y, Berendse HW, Berg D, Bhatia K, de Bie RM, Biffi A, Bloem B, Bochdanovits Z, Bonin M, Bras JM, Brockmann K, Brooks J, Burn DJ, Charlesworth G, Chen H, Chinnery PF, Chong S, Clarke CE, Cookson MR, Cooper JM, Corvol JC, Counsell C, Damier P, Dartigues JF, Deloukas P, Deuschl G, Dexter DT, van Dijk KD, Dillman A, Durif F, Dürr A, Edkins S, Evans JR, Foltynie T, Dong J, Gardner M, Gibbs JR, Goate A, Gray E, Guerreiro R, Harris C, van Hilten JJ, Hofman A, Hollenbeck A, Holton J, Hu M, Huang X, Wurster I, Mätzler W, Hudson G, Hunt SE, Huttenlocher J, Illig T, Jónsson PV, Lambert JC, Langford C, Lees A, Lichtner P, Limousin P, Lopez G, Lorenz D, McNeill A, Moorby C, Moore M, Morris HR, Morrison KE, Mudanohwo E, O'Sullivan SS, Pearson J, Perlmutter JS, Pétursson H, Pollak P, Post B, Potter S, Ravina B, Revesz T, Riess O, Rivadeneira F, Rizzu P, Ryten M, Sawcer S, Schapira A, Scheffer H, Shaw K, Shoulson I, Sidransky E, Smith C, Spencer CC, Stefánsson H, Bettella F, Stockton JD, Strange A, Talbot K, Tanner CM, Tashakkori-Ghanbaria A, Tison F, Trabzuni D, Traynor BJ, Uitterlinden AG, Velseboer D, Vidailhet M, Walker R, van de Warrenburg B, Wickremaratchi M, Williams N, Williams-Gray CH, Winder-Rhodes S, Stefánsson K, Martinez M, Wood NW, Hardy J, Heutink P, Brice A, Gasser T, Singleton AB, Factor S, Higgins D, Evans S, Shill H, Stacy M, Danielson J, Marlor L, Williamson K, Jankovic J, Hunter C, Simon D, Ryan P, Scollins L, Saunders-Pullman R, Boyar K, Costan-Toth C, Ohmann E, Sudarsky L, Joubert C, Friedman J, Chou K, Fernandez H, Lannon M, Galvez-Jimenez N, Podichetty A, Thompson K, Lewitt P, DeAngelis M, O'Brien C, Seeberger L, Dingmann C, Judd D, Marder K, Fraser J, Harris J, Bertoni J, Peterson C, Rezak M, Medalle G, Chouinard S, Panisset M, Hall J, Poiffaut H, Calabrese V, Roberge P, Wojcieszek J, Belden J, Jennings D, Marek K, Mendick S, Reich S, Dunlop B, Jog M, Horn C, Uitti R, Turk M, Ajax T, Mannetter J, Sethi K, Carpenter J, Dill B, Hatch L, Ligon K, Narayan S, Blindauer K, Abou-Samra K, Petit J, Elmer L, Aiken E, Davis K, Schell C, Wilson S, Velickovic M, Koller W, Phipps S, Feigin A, Gordon M, Hamann J, Licari E, Marotta-Kollarus M, Shannon B, Winnick R, Simuni T, Videnovic A, Kaczmarek A, Williams K, Wolff M, Rao J, Cook M, Fernandez M, Kostyk S, Hubble J, Campbell A, Reider C, Seward A, Camicioli R, Carter J, Nutt J, Andrews P, Morehouse S, Stone C, Mendis T, Grimes D, Alcorn-Costa C, Gray P, Haas K, Vendette J, Sutton J, Hutchinson B, Young J, Rajput A, Rajput A, Klassen L, Shirley T, Manyam B, Simpson P, Whetteckey J, Wulbrecht B, Truong D, Pathak M, Frei K, Luong N, Tra T, Tran A, Vo J, Lang A, Kleiner- Fisman G, Nieves A, Johnston L, So J, Podskalny G, Giffin L, Atchison P, Allen C, Martin W, Wieler M, Suchowersky O, Furtado S, Klimek M, Hermanowicz N, Niswonger S, Shults C, Fontaine D, Aminoff M, Christine C, Diminno M, Hevezi J, Dalvi A, Kang U, Richman J, Uy S, Young J, Dalvi A, Sahay A, Gartner M, Schwieterman D, Hall D, Leehey M, Culver S, Derian T, Demarcaida T, Thurlow S, Rodnitzky R, Dobson J, Lyons K, Pahwa R, Gales T, Thomas S, Shulman L, Reich S, Weiner W, Dustin K, Lyons K, Singer C, Koller W, Weiner W, Zelaya L, Tuite P, Hagen V, Rolandelli S, Schacherer R, Kosowicz J, Gordon P, Werner J, Serrano C, Roque S, Kurlan R, Berry D, Gardiner I, Hauser R, Sanchez-Ramos J, Zesiewicz T, Delgado H, Price K, Rodriguez P, Wolfrath S, Pfeiffer R, Davis L, Pfeiffer B, Dewey R, Hayward B, Johnson A, Meacham M, Estes B, Walker F, Hunt V, O'Neill C, Racette B, Swisher L, Dijamco C, Conley ED, Dorfman E, Tung JY, Hinds DA, Mountain JL, Wojcicki A, Lew M, Suchowersky O, Klein C, Golbe L, Growdon J, Wooten GF, Watts R, Guttman M, Racette B, Marlor L, Shill H, Singer C, Goldwurm S, Saint-Hilaire MH, Baker K, Litvan I, Nicholson G, Nance M, Drasby E, Isaacson S, Burn D, Pramstaller P, Al-hinti J, Moller A, Sherman S, Roxburgh R, Slevin J, Perlmutter J, Mark MH, Huggins N, Pezzoli G, Massood T, Itin I, Corbett A, Chinnery P, Ostergaard K, Snow B, Cambi F, Kay D, Samii A, Nutt J, Agarwal P, Roberts JW, Higgins DS, Molho E, Rosen A, Montimurro J, Martinez E, Griffith A, Kusel V, Yearout D, Factor S, Zabetian C, Clark LN, Liu X, Lee JH, Taub RC, Marder K, Louis ED, Cote LJ, Waters C, Ford B, Fahn S, Vance JM, Beecham GW, Martin ER, Nuytemans K, Pericak-Vance MA, Haines JL, DeStefano A, Seshadri S, Choi SH, Frank S, Bis JC, Psaty BM, Rice K, Longstreth WT Jr, Ton TG, Jain S, Ikram M, van Duijn CM, Hofman A, Uitterlinden AG, Verlinden VJ, Koudstaal PJ, Singleton A, Cookson M, Gibbs J, Hernandez D, Dillman A, Nalls M, Zonderman A, Arepalli S, Ferrucci L, Johnson R, Longo D, O'Brien R, Traynor B, Troncoso J, van der Brug M, Zielke R, Hardy J, Weale M, Ryten M, Ramasamy A, Trabzuni D, Smith C, Walker R, Kara E, Xiromerisiou G, Dardiotis E, Tsimourtou V, Spanaki C, Plaitakis A, Bozi M, Stefanis L, Vassilatis D, Koutsis G, Panas M, Houlden H, Hadjigeorgiou GM, Guerreiro R, Lunnon K, Lupton M, Powell J, Parkkinen L, Ansorge O, Hardy J.

Abstract

We conducted a meta-analysis of Parkinson's disease genome-wide association studies using a common set of 7,893,274 variants across 13,708 cases and 95,282 controls. Twenty-six loci were identified as having genome-wide significant association; these and 6 additional previously reported loci were then tested in an independent set of 5,353 cases and 5,551 controls. Of the 32 tested SNPs, 24 replicated, including 6 newly identified loci. Conditional analyses within loci showed that four loci, including GBA, GAK-DGKQ, SNCA and the HLA region, contain a secondary independent risk variant. In total, we identified and replicated 28 independent risk variants for Parkinson's disease across 24 loci. Although the effect of each individual locus was small, risk profile analysis showed substantial cumulative risk in a comparison of the highest and lowest quintiles of genetic risk (odds ratio (OR) = 3.31, 95% confidence interval (CI) = 2.55-4.30; P = 2 × 10(-16)). We also show six risk loci associated with proximal gene expression or DNA methylation.

PMID:
25064009
PMCID:
PMC4146673
DOI:
10.1038/ng.3043
[Indexed for MEDLINE]
Free PMC Article

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