Genome-Wide Association Study Confirms SNPs in SNCA and the MAPT Region as Common Risk Factors for Parkinson Disease

被引:366
作者
Edwards, Todd L. [1 ,2 ,3 ]
Scott, William K. [1 ,2 ]
Almonte, Cherylyn [1 ,2 ]
Burt, Amber [1 ,2 ]
Powell, Eric H. [1 ,2 ]
Beecham, Gary W. [1 ,2 ]
Wang, Liyong [1 ,2 ]
Zuchner, Stephan [1 ,2 ]
Konidari, Ioanna [1 ,2 ]
Wang, Gaofeng [1 ,2 ]
Singer, Carlos [5 ]
Nahab, Fatta [5 ]
Scott, Burton [6 ]
Stajich, Jeffrey M. [6 ]
Pericak-Vance, Margaret [1 ,2 ]
Haines, Jonathan [4 ]
Vance, Jeffery M. [1 ,2 ]
Martin, Eden R. [1 ,2 ]
机构
[1] Univ Miami, John P Hussman Inst Human Genom, Miami, FL 33136 USA
[2] Univ Miami, John T Macdonald Fdn Dept Human Genet, Miller Sch Med, Miami, FL 33136 USA
[3] Vanderbilt Univ, Sch Med, Div Epidemiol, Vanderbilt Epidemiol Ctr,Dept Med, Nashville, TN USA
[4] Vanderbilt Univ, Med Ctr, Ctr Human Genet Res, Nashville, TN USA
[5] Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA
[6] Duke Univ, Med Ctr, Dept Med, Durham, NC 27706 USA
基金
美国国家卫生研究院;
关键词
Parkinson disease; association study; alpha-synuclein; microtubule associated protein tau; MITOCHONDRIAL-DNA POLYMORPHISMS; PROGRESSIVE SUPRANUCLEAR PALSY; ALPHA-SYNUCLEIN; TAU-GENE; NEUROPATHOLOGIC CRITERIA; LINKAGE DISEQUILIBRIUM; PROTEIN-TAU; HAPLOTYPE; MUTATIONS; SUSCEPTIBILITY;
D O I
10.1111/j.1469-1809.2009.00560.x
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
P>Parkinson disease (PD) is a chronic neurodegenerative disorder with a cumulative prevalence of greater than one per thousand. To date three independent genome-wide association studies (GWAS) have investigated the genetic susceptibility to PD. These studies implicated several genes as PD risk loci with strong, but not genome-wide significant, associations. In this study, we combined data from two previously published GWAS of Caucasian subjects with our GWAS of 604 cases and 619 controls for a joint analysis with a combined sample size of 1752 cases and 1745 controls. SNPs in SNCA (rs2736990, p-value = 6.7 x 10-8; genome-wide adjusted p = 0.0109, odds ratio (OR) = 1.29 [95% CI: 1.17-1.42] G vs. A allele, population attributable risk percent (PAR%) = 12%) and the MAPT region (rs11012, p-value = 5.6 x 10-8; genome-wide adjusted p = 0.0079, OR = 0.70 [95% CI: 0.62-0.79] T vs. C allele, PAR% = 8%) were genome-wide significant. No other SNPs were genome-wide significant in this analysis. This study confirms that SNCA and the MAPT region are major genes whose common variants are influencing risk of PD.
引用
收藏
页码:97 / 109
页数:13
相关论文
共 102 条
  • [1] ABECASIS G, 2007, METAL METAANAL UNPUB
  • [2] Smoking and Parkinson's disease: Systematic review of prospective studies
    Allam, MF
    Campbell, MJ
    Hofman, A
    Del Castillo, AS
    Navajas, RFC
    [J]. MOVEMENT DISORDERS, 2004, 19 (06) : 614 - 621
  • [3] TESTS FOR LINEAR TRENDS IN PROPORTIONS AND FREQUENCIES
    ARMITAGE, P
    [J]. BIOMETRICS, 1955, 11 (03) : 375 - 386
  • [4] Mitochondrial DNA polymorphisms as risk factors for Parkinson's disease and Parkinson's disease dementia
    Autere, J
    Moilanen, JS
    Finnilä, S
    Soininen, H
    Mannermaa, A
    Hartikainen, P
    Hallikainen, M
    Majamaa, K
    [J]. HUMAN GENETICS, 2004, 115 (01) : 29 - 35
  • [5] Beal M Flint, 2007, Novartis Found Symp, V287, P183
  • [6] Genome-wide Association Study Implicates a Chromosome 12 Risk Locus for Late-Onset Alzheimer Disease
    Beecham, Gary W.
    Martin, Eden R.
    Li, Yi-Ju
    Slifer, Michael A.
    Gilbert, John R.
    Haines, Jonathan L.
    Pericak-Vance, Margaret A.
    [J]. AMERICAN JOURNAL OF HUMAN GENETICS, 2009, 84 (01) : 35 - 43
  • [7] Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism
    Bonifati, V
    Rizzu, P
    van Baren, MJ
    Schaap, O
    Breedveld, GJ
    Krieger, E
    Dekker, MCJ
    Squitieri, F
    Ibanez, P
    Joosse, M
    van Dongen, JW
    Vanacore, N
    van Swieten, JC
    Brice, A
    Meco, G
    van Duijn, CM
    Oostra, BA
    Heutink, P
    [J]. SCIENCE, 2003, 299 (5604) : 256 - 259
  • [8] Cabin DE, 2002, J NEUROSCI, V22, P8797
  • [9] α-synuclein locus duplication as a cause of familial Parkinson's disease
    Chartier-Harlin, MC
    Kachergus, J
    Roumier, C
    Mouroux, V
    Douay, X
    Lincoln, S
    Levecque, C
    Larvor, L
    Andrieux, J
    Hulihan, M
    Waucquier, N
    Defebvre, L
    Amouyel, P
    Farrer, M
    Destée, A
    [J]. LANCET, 2004, 364 (9440) : 1167 - 1169
  • [10] Replication of association between ELAVL4 and Parkinson disease:: the GenePD study
    DeStefano, Anita L.
    Latourelle, Jeanne
    Lew, Mark F.
    Suchowersky, Oksana
    Klein, Christine
    Golbe, Lawrence I.
    Mark, Margery H.
    Growdon, John H.
    Wooten, G. Fredrick
    Watts, Ray
    Guttman, Mark
    Racette, Brad A.
    Perlmutter, Joel S.
    Marlor, Lynn
    Shill, HollyA.
    Singer, Carlos
    Goldwurm, Stefano
    Pezzoli, Gianni
    Saint-Hilaire, Marie H.
    Hendricks, Audrey E.
    Gower, Adam
    Williamson, Sally
    Nagle, Michael W.
    Wilk, Jemma B.
    Massood, Tiffany
    Huskey, Karen W.
    Baker, Kenneth B.
    Itin, Ilia
    Litvan, Irene
    Nicholson, Garth
    Corbett, Alastair
    Nance, Martha
    Drasby, Edward
    Isaacson, Stuart
    Burn, David J.
    Chinnery, Patrick F.
    Pramstaller, Peter P.
    Al-hinti, Jomana
    Moller, Anette T.
    Ostergaard, Karen
    Sherman, Scott J.
    Roxburgh, Richard
    Snow, Barry
    Slevin, John T.
    Cambi, Franca
    Gusella, James F.
    Myers, Richard H.
    [J]. HUMAN GENETICS, 2008, 124 (01) : 95 - 99