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. 2015 May;30(6):850-4.
doi: 10.1002/mds.26192. Epub 2015 Mar 17.

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

Mike A Nalls  1 , Valentina Escott-Price  2 , Nigel M Williams  2 , Steven Lubbe  3 , Margaux F Keller  4 , Huw R Morris  3 , Andrew B Singleton  1 ; International Parkinson's Disease Genomics Consortium (IPDGC)
Affiliations

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

Mike A Nalls et al. Mov Disord. 2015 May.

Abstract

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.

Keywords: Parkinson's disease; age at onset; genetics; statistics.

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Figures

Figure 1
Figure 1. Common genetic risk factors are associated with earlier Parkinson’s disease age at onset and differ across age at onset strata
Panel A is a plot of the regression line showing the association between genetic risk score and age at onset, with the blue line as the parameter estimate and the grey shading as the 95% confidence interval of the regression model. Panel B is the overlay of the regression model from the previous panel fitted to the actual data points. Panel C shows boxplots of cumulative genetic risk estimates from pooled samples by age at onset strata. Panel D is a three-dimensional “probability map” of age at onset by genetic risk score based on the regression model.
See this image and copyright information in PMC

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