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Updated: Apr 16, 2026

Gene-environment Interaction Models to Unmask Susceptibility Mechanisms in Parkinson's Disease
Published on: January 7, 2014
Genetic risk and age in Parkinson's disease: Continuum not stratum
Mike A Nalls1, Valentina Escott-Price2, Nigel M Williams2
1Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
Background:
Recent 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.
Methods:
Genetic risk scores from these loci were calculated for 6,249 cases. Linear regression tested associations between cumulative genetic risk and PD age at onset.
Results:
Increasing genetic risk scores were associated with earlier age at onset (beta = -0.10, P = 2.92 × 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).
Conclusions:
Common genetic risk factors have a small but consistent association with AAO in PD.
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