Genetic risk of Parkinson's disease in the general population.
We investigated whether a risk score based on genetic risk variants for Parkinson's disease (PD) is associated with the risk and improves prediction of incident PD, and whether the risk score is associated with basic activities of daily living (BADL) in healthy individuals.



Within the population-based Rotterdam Study, we genotyped 26 independent risk variants for PD and constructed a genetic risk score in 7167 participants who were free of parkinsonism and dementia at baseline (1990 or 2000). Participants were followed for a maximum of twenty years for the onset of parkinsonism, dementia or death until January 1, 2011 (median follow-up 12.1 years). We studied the relationship between the genetic risk score and incident PD with adjustment for age, sex, smoking and parental history. In an independent sample of 2997 persons free of parkinsonism and dementia, we studied whether the PD risk score was associated with impaired BADL.



During follow-up (median 12.1 years), 99 persons were diagnosed with incident PD. The genetic risk score was associated with incident PD (hazard ratio per standard deviation risk 1.25 [95% confidence interval = 1.02; 1.55]), but did not substantially improve prediction (change in C-statistic 0.687 [0.628; 0.745] to 0.698 [0.635; 0.760], ΔC = 0.011 [-0.011; 0.033]). The genetic risk score was associated with a higher probability of any impairment in BADL (odds ratio = 1.11 [1.00; 1.23]).



Genetic variants for PD are associated with the risk of incident PD in the general population and with impairment in daily functioning in individuals without clinical parkinsonism, but do not improve the clinical prediction of PD. However, we were probably underpowered to detect a small improvement in PD prediction.
Department of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
Sirwan K L
SK
Darweesh
Department of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Radiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
Vincentius J A
VJ
Verlinden
Department of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Radiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
Hieab H H
HH
Adams
Department of Internal Medicine, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
André G
AG
Uitterlinden
Department of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
Albert
A
Hofman
Department of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands; Inspectorate for Health Care, The Hague, The Netherlands.
Bruno H
BH
Stricker
Department of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
Cornelia M
CM
van Duijn
Department of Neurology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
Peter J
PJ
Koudstaal
Department of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Radiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Neurology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands. Electronic address: m.a.ikram@erasmusmc.nl.
M Arfan
MA
Ikram
D000203:Activities of Daily Living / Q000523:psychology*; D000368:Aged; D000369:Aged, 80 and over; D018672:Community Health Planning; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D010300:Parkinson Disease / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology*; D012307:Risk Factors
Epidemiology; Genetic association study; Parkinson’s disease