Association of SNCA with Parkinson: Replication in the Harvard NeuroDiscovery Center Biomarker Study§

Authors

  • Hongliu Ding MD, PhD, MPH,

    1. Center for Neurologic Diseases, Harvard Medical School and Brigham & Women's Hospital, Cambridge, Massachusetts, USA
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  • Alison K. Sarokhan,

    1. Center for Neurologic Diseases, Harvard Medical School and Brigham & Women's Hospital, Cambridge, Massachusetts, USA
    2. Harvard NeuroDiscovery Center Biomarker Program, Harvard Medical School, Cambridge, Massachusetts, USA
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  • Sarah S. Roderick,

    1. Center for Neurologic Diseases, Harvard Medical School and Brigham & Women's Hospital, Cambridge, Massachusetts, USA
    2. Harvard NeuroDiscovery Center Biomarker Program, Harvard Medical School, Cambridge, Massachusetts, USA
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  • Rachit Bakshi PhD,

    1. Center for Neurologic Diseases, Harvard Medical School and Brigham & Women's Hospital, Cambridge, Massachusetts, USA
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  • Nancy E. Maher MPH,

    1. Center for Neurologic Diseases, Harvard Medical School and Brigham & Women's Hospital, Cambridge, Massachusetts, USA
    2. Harvard NeuroDiscovery Center Biomarker Program, Harvard Medical School, Cambridge, Massachusetts, USA
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  • Paymon Ashourian,

    1. Center for Neurologic Diseases, Harvard Medical School and Brigham & Women's Hospital, Cambridge, Massachusetts, USA
    2. Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
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  • Caroline G. Kan,

    1. Center for Neurologic Diseases, Harvard Medical School and Brigham & Women's Hospital, Cambridge, Massachusetts, USA
    2. Harvard NeuroDiscovery Center Biomarker Program, Harvard Medical School, Cambridge, Massachusetts, USA
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  • Sunny Chang,

    1. Center for Neurologic Diseases, Harvard Medical School and Brigham & Women's Hospital, Cambridge, Massachusetts, USA
    2. Harvard NeuroDiscovery Center Biomarker Program, Harvard Medical School, Cambridge, Massachusetts, USA
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  • Andrea Santarlasci,

    1. Harvard NeuroDiscovery Center Biomarker Program, Harvard Medical School, Cambridge, Massachusetts, USA
    2. Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA
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  • Kyleen E. Swords,

    1. Harvard NeuroDiscovery Center Biomarker Program, Harvard Medical School, Cambridge, Massachusetts, USA
    2. Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA
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  • Bernard M. Ravina MD,

    1. Translational Neurology, Biogen Idec, Inc., Cambridge, Massachusetts, USA
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  • Michael T. Hayes MD,

    1. Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts, USA
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  • U. Shivraj Sohur MD, PhD,

    1. Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA
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  • Anne-Marie Wills MD,

    1. Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA
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  • Alice W. Flaherty MD, PhD,

    1. Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA
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  • Vivek K. Unni MD, PhD,

    1. Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA
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  • Albert Y. Hung MD, PhD,

    1. Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA
    2. Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts, USA
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  • Dennis J. Selkoe MD,

    1. Center for Neurologic Diseases, Harvard Medical School and Brigham & Women's Hospital, Cambridge, Massachusetts, USA
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  • Michael A. Schwarzschild MD, PhD,

    1. Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA
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  • Michael G. Schlossmacher MD,

    1. University of Ottawa, Ottawa, Ontario, Canada
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  • Lewis R. Sudarsky MD,

    1. Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts, USA
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  • John H. Growdon MD,

    1. Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA
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  • Adrian J. Ivinson PhD,

    1. Harvard NeuroDiscovery Center Biomarker Program, Harvard Medical School, Cambridge, Massachusetts, USA
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  • Bradley T. Hyman MD, PhD,

    1. Harvard NeuroDiscovery Center Biomarker Program, Harvard Medical School, Cambridge, Massachusetts, USA
    2. Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA
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  • Clemens R. Scherzer MD

    Corresponding author
    1. Center for Neurologic Diseases, Harvard Medical School and Brigham & Women's Hospital, Cambridge, Massachusetts, USA
    2. Harvard NeuroDiscovery Center Biomarker Program, Harvard Medical School, Cambridge, Massachusetts, USA
    3. Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA
    4. Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts, USA
    • Laboratory for Neurogenomics, Center for Neurologic Diseases, Harvard Medical School and Brigham & Women's Hospital, 65 Landsdowne Street, Suite 307A, Cambridge, MA 02139, USA
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  • Funding agencies: This study was funded by NIH grants R01 NS064155 (to C.R.S.), R21 NS060227 (to C.R.S.), K24 NS060991 (to M.A.S.), the Harvard NeuroDiscovery Center (to C.R.S. and B.T.H.), the Michael J. Fox Foundation (grants to C.R.S., M.G.S., and J.H.G.), the M.E.M.O. Hoffman Foundation (to C.R.S.), and the RJG Foundation (to C.R.S.).

  • Relevant conflicts of interest/financial disclosures: Clemens R. Scherzer is a consultant for Link Medicine Corp and the Michael J. Fox Foundation and a scientific collaborator of DiaGenic and Pfizer. Alice W. Flaherty has a contract with Neurologix, Inc.

  • §

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

Abstract

Background:

Mutations in the α-synuclein gene (SNCA) cause autosomal dominant forms of Parkinson's disease, but the substantial risk conferred by this locus to the common sporadic disease has only recently emerged from genome-wide association studies.

Methods:

We genotyped a prioritized noncoding variant in SNCA intron 4 in 344 patients with Parkinson's disease and 275 controls from the longitudinal Harvard NeuroDiscovery Center Biomarker Study.

Results:

The common minor allele of rs2736990 was associated with elevated disease susceptibility (odds ratio, 1.40; P = .0032).

Conclusions:

This result increases confidence in the notion that in many clinically well-characterized patients, genetic variation in SNCA contributes to “sporadic” disease. © 2011 Movement Disorder Society

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