Genetic risk factors in Finnish patients with Parkinson's disease

: Susanna Ylönen, Ari Siitonen, Michael A. Nalls, Pauli Ylikotila, Jaana Autere, Johanna Eerola-Rautio, Raphael Gibbs, Mikko Hiltunen, Pentti J. Tienari, Hilkka Soininen, Andrew B. Singleton, Kari Majamaa

Publisher: Elsevier Ltd

: 2017

: Parkinsonism and Related Disorders

: 45

: 39

: 43

: 5

: 1353-8020

DOI: https://doi.org/10.1016/j.parkreldis.2017.09.021

Introduction

Variation contributing to the risk of Parkinson's disease (PD) has been identified in several genes and at several loci including GBA, SMPD1, LRRK2, POLG1, CHCHD10 and MAPT,
but the frequencies of risk variants seem to vary according to ethnic
background. Our aim was to analyze how variation in these genes
contributes to PD in the Finnish population.

Methods

The
subjects consisted of 527 Finnish patients with early-onset PD, 325
patients with late-onset PD and 403 population controls. We screened for
known genetic risk variants in GBA, SMPD1, LRRK2, POLG1, CHCHD10 and MAPT. In addition, DNA from 225 patients with early-onset Parkinson's disease was subjected to whole exome sequencing (WES).

Results

We detected a significant difference in the length variation of the CAG repeat in POLG1 between patients with early-onset PD compared to controls. The p.N370S and p.L444P variants in GBA contributed to a relative risk of 3.8 in early-onset PD and 2.5 in late-onset PD. WES revealed five variants in LRRK2 and SMPD1
that were found in the patients but not in the Finnish ExAC sequences.
These are possible risk variants that require further confirmation. The
p.G2019S variant in LRRK2, common in North African Arabs and Ashkenazi Jews, was not detected in any of the 849 PD patients.

Conclusions

The POLG1 CAG repeat length variation and the GBA p.L444P variant are associated with PD in the Finnish population.