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

Shannon K. McDonnell, Daniel J Schaid, Alexis Elbaz, Kari J. Strain, James Howard Bower, J. Eric Ahlskog, Demetrius M. Maraganore, Walter A Rocca

Research output: Contribution to journalArticle

31 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)788-795
Number of pages8
JournalAnnals of Neurology
Volume59
Issue number5
DOIs
StatePublished - May 2006

Fingerprint

Parkinson Disease
Penetrance
Referral and Consultation
Parkinsonian Disorders
Proxy
Population
Genes
Medical Records
Cluster Analysis
Cohort Studies
Alleles

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Complex segregation analysis of Parkinson's disease : The Mayo Clinic Family Study. / McDonnell, Shannon K.; Schaid, Daniel J; Elbaz, Alexis; Strain, Kari J.; Bower, James Howard; Ahlskog, J. Eric; Maraganore, Demetrius M.; Rocca, Walter A.

In: Annals of Neurology, Vol. 59, No. 5, 05.2006, p. 788-795.

Research output: Contribution to journalArticle

McDonnell, Shannon K. ; Schaid, Daniel J ; Elbaz, Alexis ; Strain, Kari J. ; Bower, James Howard ; Ahlskog, J. Eric ; Maraganore, Demetrius M. ; Rocca, Walter A. / Complex segregation analysis of Parkinson's disease : The Mayo Clinic Family Study. In: Annals of Neurology. 2006 ; Vol. 59, No. 5. pp. 788-795.
@article{e2a70f3519ba4b9688dc368077a28b5d,
title = "Complex segregation analysis of Parkinson's disease: The Mayo Clinic Family Study",
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.",
author = "McDonnell, {Shannon K.} and Schaid, {Daniel J} and Alexis Elbaz and Strain, {Kari J.} and Bower, {James Howard} and Ahlskog, {J. Eric} and Maraganore, {Demetrius M.} and Rocca, {Walter A}",
year = "2006",
month = "5",
doi = "10.1002/ana.20844",
language = "English (US)",
volume = "59",
pages = "788--795",
journal = "Annals of Neurology",
issn = "0364-5134",
publisher = "John Wiley and Sons Inc.",
number = "5",

}

TY - JOUR

T1 - Complex segregation analysis of Parkinson's disease

T2 - The Mayo Clinic Family Study

AU - McDonnell, Shannon K.

AU - Schaid, Daniel J

AU - Elbaz, Alexis

AU - Strain, Kari J.

AU - Bower, James Howard

AU - Ahlskog, J. Eric

AU - Maraganore, Demetrius M.

AU - Rocca, Walter A

PY - 2006/5

Y1 - 2006/5

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=33646384570&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33646384570&partnerID=8YFLogxK

U2 - 10.1002/ana.20844

DO - 10.1002/ana.20844

M3 - Article

C2 - 16634030

AN - SCOPUS:33646384570

VL - 59

SP - 788

EP - 795

JO - Annals of Neurology

JF - Annals of Neurology

SN - 0364-5134

IS - 5

ER -