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Common variation in the LRRK2 gene is a risk factor for Parkinson's disease

Authors

  • Ignacio F. Mata PhD,

    Corresponding author
    1. Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA
    2. Department of Neurology, University of Washington School of Medicine, Seattle, Washington, USA
    • Geriatric Research Education and Clinical Center S-182, VA Puget Sound Health Care System, 1660 South Columbian Way, Seattle, WA 98108, USA

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  • Harvey Checkoway PhD,

    1. Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington, USA
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  • Carolyn M. Hutter PhD,

    1. Department of Epidemiology, University of Washington, Seattle, Washington, USA
    2. Cancer Prevention Program, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
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  • Ali Samii MD,

    1. Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA
    2. Department of Neurology, University of Washington School of Medicine, Seattle, Washington, USA
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  • John W. Roberts MD,

    1. Virginia Mason Medical Center, Seattle, Washington, USA
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  • Hojoong M. Kim MD,

    1. Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA
    2. Department of Neurology, University of Washington School of Medicine, Seattle, Washington, USA
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  • Pinky Agarwal MD,

    1. Booth Gardner Parkinson's Care Center, Evergreen Hospital Medical Center, Kirkland, Washington, USA
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  • Victoria Alvarez PhD,

    1. Laboratorio de Genetica Molecular, Instituto de Investigacion Nefrologica (IRSINFRIAT), Hospital Universitario Central de Asturias, Oviedo, Spain
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  • Renee Ribacoba MD,

    1. Department of Neurology, Hospital Universitario Central de Asturias, Oviedo, Spain
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  • Pau Pastor MD, PhD,

    1. Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, University of Navarra, Pamplona, Spain
    2. Department of Neurology, Clínica Universidad de Navarra, University of Navarra School of Medicine, Pamplona, Spain
    3. CIBERNED, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Spain
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  • Oswaldo Lorenzo-Betancor MD,

    1. Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, University of Navarra, Pamplona, Spain
    2. Department of Neurology, Clínica Universidad de Navarra, University of Navarra School of Medicine, Pamplona, Spain
    3. CIBERNED, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Spain
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  • Jon Infante MD,

    1. CIBERNED, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Spain
    2. Department of Neurology, “Marques de Valdecilla” University Hospital, Santander, Spain
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  • María Sierra MD,

    1. Department of Neurology, “Marques de Valdecilla” University Hospital, Santander, Spain
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  • Pilar Gómez-Garre PhD,

    1. CIBERNED, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Spain
    2. Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain
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  • Pablo Mir MD, PhD,

    1. CIBERNED, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Spain
    2. Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain
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  • Beate Ritz MD, PhD,

    1. Department of Epidemiology, School of Public Health, University of California Los Angeles, Los Angeles, California, USA
    2. Department of Environmental Health Sciences, School of Public Health, University of California Los Angeles, Los Angeles, California, USA
    3. Department of Neurology, School of Medicine, University of California Los Angeles, Los Angeles, California, USA
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  • Shannon L. Rhodes PhD,

    1. Department of Epidemiology, School of Public Health, University of California Los Angeles, Los Angeles, California, USA
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  • Amy Colcher MD,

    1. Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
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  • Vivianna Van Deerlin MD, PhD,

    1. Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
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  • Kathryn A. Chung MD,

    1. Department of Neurology, Oregon Health and Science University, Portland, Oregon, USA
    2. Portland VA Medical Center, Portland, Oregon, USA
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  • Joseph F. Quinn MD,

    1. Department of Neurology, Oregon Health and Science University, Portland, Oregon, USA
    2. Portland VA Medical Center, Portland, Oregon, USA
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  • Dora Yearout BS,

    1. Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA
    2. Department of Neurology, University of Washington School of Medicine, Seattle, Washington, USA
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  • Erica Martinez BS,

    1. Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA
    2. Department of Neurology, University of Washington School of Medicine, Seattle, Washington, USA
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  • Federico M. Farin MD,

    1. Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington, USA
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  • Jia Y. Wan MS,

    1. Department of Epidemiology, University of Washington, Seattle, Washington, USA
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  • Karen L. Edwards PhD,

    1. Department of Epidemiology, University of Washington, Seattle, Washington, USA
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  • Cyrus P. Zabetian MD, MS

    Corresponding author
    1. Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA
    2. Department of Neurology, University of Washington School of Medicine, Seattle, Washington, USA
    • Geriatric Research Education and Clinical Center S-182, VA Puget Sound Health Care System, 1660 South Columbian Way, Seattle, WA 98108, USA

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  • Relevant conflicts of interest/financial disclosures: Nothing to report.

  • Full financial disclosures and author roles may be found in the online version of this article.

Abstract

Background:

Common variants in the LRRK2 gene influence the risk of Parkinson's disease (PD) in Asians, but whether the same is true in European-derived populations is less clear.

Methods:

We genotyped 66 LRRK2 tagging single-nucleotide polymorphisms (SNPs) in 575 PD patients and 689 controls from the northwestern United States (tier 1). PD-associated SNPs (P < .05) were then genotyped in an independent sample of 3617 cases and 2512 controls from the United States and Spain (tier 2). Logistic regression was used to model additive SNP genotype effects adjusted for age and sex among white individuals.

Results:

Two regions showed independent association with PD in tier 1, and SNPs in both regions were successfully replicated in tier 2 (rs10878226, combined odds ratio [OR], 1.20; 95% confidence interval [CI], 1.08–1.33; P = 6.3 × 10−4; rs11176013, OR, 0.89; CI, 0.83–0.95; P = 4.6 × 10−4).

Conclusions:

Our data suggest that common variation within LRRK2 conveys susceptibility for PD in individuals of European ancestry. © 2012 Movement Disorder Society

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