Parkinson's disease: from genetics to clinical practice

Abstract

Breakthroughs in genetics over the last decade have radically advanced our understanding of the etiological basis of Parkinson's disease (PD). Although much research remains to be done, the main genetic causes of this neurodegenerative disorder are now partially unraveled, allowing us to feel more confident that our knowledge about the genetic architecture of PD will continue to increase exponentially. How and when these discoveries will be introduced into general clinical practice, however, remains uncertain. In this review, we provide a general summary of the progress in the genetics of PD and discuss how this knowledge will contribute to the diagnosis and clinical management of patients with, or at risk of this disorder.

Keywords: Clinical genetics; Genetic risk factor.; Genetic testing; Genetics; Mendelian genes; PARK; Parkinson's disease.

Fig. (1)

Schematic representation of the genetic architecture of PD. The Y axis shows the strength of genetic effects and the X axis indicates the age at onset of disease. Autosomal recessive genes are presented in yellow; autosomal dominant genes in blue and risk loci in green. The size of each circle is an approximation of the population attributable risk (PAR), that is, the proportion of PD that is ascribable to a mutation or a genetic risk variant at any gene. Percentages of PAR in genetic risk loci are based on references 56, 59 and 79. For genes related to monogenic forms of disease (PLA2G6, ATP13A2, FBOX7, PARK2, PINK1, DJ1, SNCA and VPS35) % of PAR have limited value due to the rarity of the deleterious alleles in the population and therefore the circle size represents an approximation of the % of cases due to known genetic causes. Relative risks for each loci are based on evidence from the PD gene database (www.pdgene.org).