The genetics of behavior and cognition in Parkinson’s disease


Since the identification of a mutation in the α-synuclein gene in families with Parkinson’s disease (PD) in 1997 [1], a wealth of further research has increased our knowledge of the genetic basis of PD. It has become apparent that a single causative gene cannot fully explain the disease, but rather its genetic etiology is heterogeneous, with six causative genes well established to date in studies of Mendelian forms of PD (α-synuclein [SNCA], leucine-rich repeat kinase 2 [LRRK2], parkin [PARK2], PTEN-induced kinase-1 [PINK1], DJ-1, ATP13A2), and multiple other loci implicated [2]. However, these genes probably account for only 2-3% of PD cases [3]. In the vast majority of sporadic cases, the etiology appears to be more complex, resulting from a combination of multiple environmental and genetic risk factors [4]. Four susceptibility genes, within which common variation increases disease risk, have now been well validated: these include LRRK2, SNCA, the microtubule-associated protein tau gene (MAPT) and the glucocerebrosidase gene (GBA) [2]. Recently, a further 13 genetic risk loci have been identified through genome-wide association studies [5,6].