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Genetic risk and age in Parkinson's disease: Continuum not stratum
Author(s) -
Nalls Mike A.,
EscottPrice Valentina,
Williams Nigel M.,
Lubbe Steven,
Keller Margaux F.,
Morris Huw R.,
Singleton Andrew B.
Publication year - 2015
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.26192
Subject(s) - age of onset , disease , parkinson's disease , genetic predisposition , medicine , genome wide association study , genetic association , genetic model , genetics , biology , single nucleotide polymorphism , genotype , gene
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. © 2015 International Parkinson and Movement Disorder Society