Format

Send to

Choose Destination
Mov Disord. 2015 May;30(6):847-50. doi: 10.1002/mds.26237. Epub 2015 Apr 25.

Impact of Parkinson's disease risk loci on age at onset.

Author information

1
Platform for Genome Analytics, Institutes of Neurogenetics & Integrative and Experimental Genomics, University of Lübeck, Lübeck, Germany.
2
Institute of Cancer Epidemiology, Danish Cancer Society Research Center, Copenhagen, Denmark.
3
Department of Epidemiology and Environmental Sciences, School of Public Health, University of California, Los Angeles, California, USA.
4
Institute for Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center Mainz, Mainz, Germany.
5
School of Public Health, Faculty of Medicine, The Imperial College of Science, Technology, and Medicine, London, UK.

Abstract

BACKGROUND:

The aim of this study was to assess whether recently identified Parkinson's disease (PD) risk genes also influence age at onset in PD.

METHODS:

We genotyped 23 single-nucleotide polymorphisms in 1,526 Danish PD patients and performed linear regression analyses with age at onset. The combined impact of PD risk loci on age at onset was assessed by linear regression analyses using a weighted genetic risk score.

RESULTS:

The strongest effects were observed with rs12726330 in GBA (beta = -3.63, P = 2.0 × 10(-5) ) and rs34311866 in TMEM175/GAK (beta = -1.19, P = 4.0 × 10(-3) ), corresponding to a 3.6-y and 1.2-y decrease of age at onset per risk allele, respectively. The weighted genetic risk score yielded significant association with reduced onset age (P = 3.98 × 10(-3) ), although the variance explained was small (0.6%), and the effect was mostly driven by polymorphisms in GBA and TMEM175/GAK.

CONCLUSIONS:

Overall, our study indicates that GBA and TMEM175/GAK significantly alter age at onset in PD.

KEYWORDS:

DGKQ; GAK; GBA; N370S; Parkinson's disease, PD; age at onset; genetic association; genetic risk score; genome-wide association study, GWAS

PMID:
25914293
DOI:
10.1002/mds.26237
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center