Genetic risk and age in Parkinson's disease: Continuum not stratum

BackgroundRecent genomewide association study meta-analyses have identified 28 loci associated with risk of Parkinson's disease (PD). We sought to investigate whether these genetic risk factors are associated with PD age at onset. MethodsGenetic risk scores from these loci were calculated for 6,249 cases. Linear regression tested associations between cumulative genetic risk and PD age at onset. ResultsIncreasing genetic risk scores were associated with earlier age at onset (beta=-0.10, P=2.92 x 10(-8), adjusted r(2)=0.27). Single standard deviation increase in genetic risk score is associated with 37.44 d earlier age at onset. Highest genetic risk was found at 31 to 60 y, onset slightly below average age at onset (AAO). ConclusionsCommon genetic risk factors have a small but consistent association with AAO in PD. (c) 2015 International Parkinson and Movement Disorder Society