Insights on Genetic and Environmental Factors in Parkinson’s Disease from a regional Swedish Case-Control Cohort

Abstract

BACKGROUND: Risk factors for Parkinson's disease (PD) can be more or less relevant to a population due to population-specific genetic architecture, local lifestyle habits, and environmental exposures. Therefore, it is essential to study PD at a local, regional, and continental scale in order to increase the knowledge on disease etiology. OBJECTIVE: We aimed to investigate the contribution of genetic and environmental factors to PD in a new Swedish case-control cohort. METHODS: PD patients (n=929) and matched population-based controls (n=935) from the southernmost county in Sweden were included in the cohort. Information on environmental exposures was obtained using questionnaires at inclusion. Genetic analyses included a genome-wide association study (GWAS), haplotype assessment, and a risk profile analysis using cumulative genetic risk scores. RESULTS: The cohort is a representative PD case-control cohort (64% men, mean age at diagnosis = 67 years, median Hoehn and Yahr score = 2.0), in which previously reported associations between PD and environmental factors, such as tobacco, could be confirmed. We describe the first GWAS of PD solely composed of PD patients from Sweden, and confirm associations to well-established risk alleles in SNCA. In addition, we identified a potential novel, population-specific PD risk variant in the PLPP4 locus (rs12771445) along with a risk haplotype in the region. CONCLUSIONS: This work provides an in-depth description of a new PD case-control cohort from southern Sweden in which we identified a potential novel PD risk locus, PLPP4. Replication studies are needed to determine whether the PLPP4 locus is associated with PD in Sweden, and on a global scale.