Complex segregation analysis of Parkinson's disease: The Mayo Clinic Family Study.
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 <or= 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.


CONCLUSIONS
The familial aggregation of PD may be explained in part by a major gene with additive effect on the penetrance.
McDonnell
Shannon K
SK
Division of Biostatistics, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Schaid
Daniel J
DJ
Elbaz
Alexis
A
Strain
Kari J
KJ
Bower
James H
JH
Ahlskog
J Eric
JE
Maraganore
Demetrius M
DM
Rocca
Walter A
WA
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D005190:Family; D005260:Female; D006801:Humans; D008297:Male; D008498:Medical Record Linkage; D008875:Middle Aged; D008910:Minnesota / Q000453:epidemiology; D015233:Models, Statistical; D010300:Parkinson Disease / Q000453:epidemiology* / Q000235:genetics; D018579:Patient Selection; D010375:Pedigree; D012306:Risk; D014481:United States / Q000453:epidemiology