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Complex segregation analysis of Parkinson's disease: The Mayo Clinic Family Study

Authors

  • Shannon K. McDonnell MS,

    1. Division of Biostatistics, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN
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  • Daniel J. Schaid PhD,

    1. Division of Biostatistics, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN
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  • Alexis Elbaz MD, PhD,

    1. Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN
    2. Institut National de la Sante et de la Recherche Médicale Unit 708, Hôpital de la Salpêtrière, Paris, France
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    • A.E. participated in this study while on leave from the Institut National de la Sante et de la Recherche Médicale Unit 360.

  • Kari J. Strain BS,

    1. Division of Biostatistics, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN
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  • James H. Bower MD,

    1. Department of Neurology, Mayo Clinic College of Medicine, Rochester, MN
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  • J. Eric Ahlskog PhD, MD,

    1. Department of Neurology, Mayo Clinic College of Medicine, Rochester, MN
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  • Demetrius M. Maraganore MD,

    1. Department of Neurology, Mayo Clinic College of Medicine, Rochester, MN
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  • Walter A. Rocca MD, MPH

    Corresponding author
    1. Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN
    2. Department of Neurology, Mayo Clinic College of Medicine, Rochester, MN
    • Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, 200 First Street SW, Rochester, MN 55905
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Abstract

Objective

To conduct complex segregation analyses of Parkinson's disease (PD).

Methods

Data on the familial aggregation of PD remain conflicting. We conducted a historical cohort study of 1,234 relatives of 162 patients with PD representative of people of Olmsted County, MN, and of 3,009 relatives of 411 patients with PD referred to the Mayo Clinic. Relatives were interviewed and screened for parkinsonism either directly or through a proxy, those who screened positive were examined, or a copy of their medical record was obtained to confirm the diagnosis. For subjects who resided in Olmsted County, additional information was obtained from the archives of the Olmsted County Historical Society and from a records-linkage system.

Results

Thirty-two relatives of population-based probands and 69 relatives of referral patients developed PD (101 in total). Combining population-based and referral samples, the model that best explained the familial clustering of PD overall was a major gene with additive effect on the penetrance. This model predicted an average decrease in age at onset of PD of approximately 18 years for each copy of the putative high-risk allele. The best fitting model for younger onset PD (age ≤ 59 years) was an autosomal recessive model. The best fitting models for older onset PD (age > 59 years) were a recessive or an additive model.

Interpretation

The familial aggregation of PD may be explained in part by a major gene with additive effect on the penetrance. Ann Neurol 2006;59:788–795

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