Sirwan K L Darweesh1, Vincentius J A Verlinden2, Hieab H H Adams2, André G Uitterlinden3, Albert Hofman1, Bruno H Stricker4, Cornelia M van Duijn1, Peter J Koudstaal5, M Arfan Ikram6. 1. Department of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands. 2. Department of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Radiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands. 3. Department of Internal Medicine, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands. 4. Department of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands; Inspectorate for Health Care, The Hague, The Netherlands. 5. Department of Neurology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands. 6. 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.
Abstract
INTRODUCTION: 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. METHODS: 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. RESULTS: 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]). CONCLUSION: 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.
INTRODUCTION: 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. METHODS: 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. RESULTS: 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]). CONCLUSION: 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.
Authors: M Arfan Ikram; Guy G O Brusselle; Sarwa Darwish Murad; Cornelia M van Duijn; Oscar H Franco; André Goedegebure; Caroline C W Klaver; Tamar E C Nijsten; Robin P Peeters; Bruno H Stricker; Henning Tiemeier; André G Uitterlinden; Meike W Vernooij; Albert Hofman Journal: Eur J Epidemiol Date: 2017-10-24 Impact factor: 8.082
Authors: Bhuvan Molparia; Brian N Schrader; Eli Cohen; Jennifer L Wagner; Sandeep R Gupta; Sherrie Gould; Nelson Hwynn; Emily G Spencer; Ali Torkamani Journal: PeerJ Date: 2018-07-20 Impact factor: 2.984
Authors: Benjamin Meir Jacobs; Daniel Belete; Jonathan Bestwick; Cornelis Blauwendraat; Sara Bandres-Ciga; Karl Heilbron; Ruth Dobson; Mike A Nalls; Andrew Singleton; John Hardy; Gavin Giovannoni; Andrew John Lees; Anette-Eleonore Schrag; Alastair J Noyce Journal: J Neurol Neurosurg Psychiatry Date: 2020-10 Impact factor: 10.154