An Overview of the Genetics of Parkinson's Disease

Genetic Classification And Etiology Of Pd

To date, the genetic identification of regions responsible for PD reached only 18 identified chromosomal loci. They are termed PARK, referring to the link to PD, and enumerated in the chronological order of their identification (PARK1, PARK2, etc.) (Draoui et al., 2020). Limited knowledge is shown through the current findings in this issue. Indeed, the list of genes related to PD is incomplete, and the current classification system shows several discrepancies(Tambasco et al., 2016). That is because the list comprises loci that could not be replicated, nor all the causative genes have yet been identified, nor do they compromise disease-determining mutations, especially because some mutations are considered genetic risk factors rather than being direct causative agents. What’s more, one locus, PARK4, has been undistinguishably classified as a new chromosomal region but has lately been found to be identical to PARK1. In addition to genome-wide association studies, it is worthy to denote that identification of the loci was based in some cases on genetic linkage within large families, while in other cases the known function of protein helped deduce the gene responsible for its production.

Over the past 20 years, mutations in other genes have been strongly associated with PD, either with autosomal dominant inheritance (LRRK2 and VPS35) or autosomal recessive inheritance (PARKIN, PINK1 and DJ1). Other genes have also been reported to be responsible for Parkinsonism or atypical PD, including ATP13A2, DNAJC6, FBXO7, GBA, PLA2G6, SPG11, SYNJ1 and VPS13C (Deng et al., 2018; Puschmann, 2017)

Figure 1.

Etiology and phenotype of Parkinson's disease (regenerated from Crosiers et al., 2011)

Monogenic variants account for only 10 to 20% of Parkinson's cases worldwide, and these mutations are more common in people over the age of 40, with a family history of PD, or with parental consanguinity (Kilarski et al., 2012; Lesage & Brice, 2009).