Uncovering common genetic risk factors for Parkinson’s disease

Abstract

Uncovering common genetic risk factors for Parkinson's disease Introduction. Mutations in the so called PARK genes lead to rare familial forms of Parkinson's disease (PD). However the extent to which common genetic variability around these genes alters risk for common PD remains unclear. The Australian Parkinson's Project is analysing genetic variability around the PARK loci in a large PD case-control sample recruited from three Australian states. The emphasis is on gene-gene and gene-environment interactions between commonly occurring variables. Aim. To report on a pilot PD association analysis of 87 polymorphisms around13 PARK genes in an initial case-control sample recruited during 2006. Methods. PD cases (n=326) and unaffected control subjects (n=298) of white European ancestry were recruited from three specialist clinics in Brisbane and the Australian Electoral Roll. Common genetic variables (86 SNPs genotyped on the TaqMan platform and 1 STR variable genotyped using standard methods) were assessed in all subjects. Haplotypes around the PARK genes were inferred by implementing the expectation-maximization algorithm using the program EH. Other statistical analyses were performed using SPSS and SNPStats. Results. Consistent with previous studies, PD cases were more likely than controls to report a family history of PD, high levels of pesticide exposure and lower frequency of cigarette smoking. The frequencies of all polymorphisms were comparable to those reported in other samples of European ancestry, although several putative haplotype tagging SNPs were highly correlated (r squared greater than 0.9) in our sample. Weak associations with PD were identified for variables around the alpha-synuclein, parkin, PINK1 and APOE genes at levels insensitive to identification by approaches such as whole-genome association analysis. Conclusion. Our initial analysis supports the validity of the recruitment strategy and experimental design being employed in this project and confirms that the individual influence of common genetic variability around the PARK genes to PD risk is modest at best. Initial analyses of interactive effects on PD outcome are now underway.