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

Authors

  • Todd L. Edwards,

    1. John P. Hussman Institute for Human Genomics and the Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, FL
    2. Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Vanderbilt University, TN
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  • William K. Scott,

    1. John P. Hussman Institute for Human Genomics and the Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, FL
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  • Cherylyn Almonte,

    1. John P. Hussman Institute for Human Genomics and the Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, FL
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  • Amber Burt,

    1. John P. Hussman Institute for Human Genomics and the Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, FL
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  • Eric H. Powell,

    1. John P. Hussman Institute for Human Genomics and the Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, FL
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  • Gary W. Beecham,

    1. John P. Hussman Institute for Human Genomics and the Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, FL
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  • Liyong Wang,

    1. John P. Hussman Institute for Human Genomics and the Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, FL
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  • Stephan Züchner,

    1. John P. Hussman Institute for Human Genomics and the Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, FL
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  • Ioanna Konidari,

    1. John P. Hussman Institute for Human Genomics and the Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, FL
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  • Gaofeng Wang,

    1. John P. Hussman Institute for Human Genomics and the Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, FL
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  • Carlos Singer,

    1. Department of Neurology, Miller School of Medicine, University of Miami, FL
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  • Fatta Nahab,

    1. Department of Neurology, Miller School of Medicine, University of Miami, FL
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  • Burton Scott,

    1. Department of Medicine, Duke University Medical Center, Duke University, NC
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  • Jeffrey M. Stajich,

    1. Department of Medicine, Duke University Medical Center, Duke University, NC
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  • Margaret Pericak-Vance,

    1. John P. Hussman Institute for Human Genomics and the Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, FL
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  • Jonathan Haines,

    1. Center for Human Genetics Research, Vanderbilt University Medical Center, Vanderbilt University, TN
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  • Jeffery M. Vance,

    1. John P. Hussman Institute for Human Genomics and the Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, FL
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  • Eden R. Martin

    Corresponding author
    1. John P. Hussman Institute for Human Genomics and the Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, FL
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*Corresponding author: Eden R. Martin, John P. Hussman Institute for Human Genomics, 1501 NW 10th Avenue, BRB 305 (M-860), Miami FL 33136. Tel: 305-243-2372; Fax: 305-243-1968; E-mail: Emartin1@med.miami.edu

Summary

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 × 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 × 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.

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