Variants in GBA, SNCA, and MAPT influence Parkinson disease risk, age at onset, and progression

We are starting to learn much more about the genetic architecture of PD and how genes determine not only ones absolute risk of acquiring PD, but also account for a substantial proportion of the heterogeneity of PD.

Neurobiol Aging. 2015 Sep 30. pii: S0197-4580(15)00471-6. doi: 10.1016/j.neurobiolaging.2015.09.014. [Epub ahead of print]

Davis AA, Andruska KM, Benitez BA, Racette BA, Perlmutter JS, Cruchaga C.

http://www.neurobiologyofaging.org/article/S0197-4580(15)00471-6/abstract

Multiple genetic variants have been linked to risk of Parkinson disease (PD), but known mutations do not explain a large proportion of the total PD cases. Similarly, multiple loci have been associated with PD risk by genome-wide association studies (GWAS). The influence that genetic factors confer on phenotypic diversity remains unclear. Few studies have been performed to determine whether the GWAS loci are also associated with age at onset (AAO) or motor progression. We used 2 PD case-control data sets (Washington University and the Parkinson's Progression Markers Initiative) to determine whether polymorphisms located at the GWAS top hits (GBA, ACMSD/TMEM163, STK39, MCCC1/LAMP3, GAK/TMEM175, SNCA, and MAPT) show association with AAO or motor progression. We found associations between single nucleotide polymorphisms at the GBA and MAPT loci and PD AAO and progression. These findings reinforce the complex genetic basis of PD and suggest that distinct genes and variants explain the genetic architecture of PD risk, onset, and progression.