The emerging genetic architecture of Parkinson’s disease
Mutations and variants in several genes have been identified to be causal or increase susceptibility to PD. Genes indicated in red, which have a very high or causal link with PD development, show Mendelian inheritance and are rare in the population. Genes indicated in orange confer a greater risk of PD development, but with incomplete penetrance. These genes have been identified through both Mendelian and GWAS studies. The expansion of GWAS targeting idiopathic PD has highlighted a plethora of common alleles, illustrated in yellow. These are very common in the population and confer a heightened susceptibility to PD development. Different PD linked mutations in LRRK2 confer varying risk of PD development and penetrance. There are protective variants in LRRK2, which significantly reduce the risk of PD development, highlighting the central role LRRK2 may play in PD pathogenesis.