Frequency of non-motor symptoms in Parkinson's disease patients carrying the E326K and T369M GBA risk variants

Variants in the GBA (glucocerebrosidase) gene are the most common genetic risk factor for the development of Parkinson's disease (PD). Depending on the variant and the population, the risk of PD is increased by 2 to 28-fold [ [1]
]. Biallelic severe and mild pathogenic variants cause Gaucher's disease, whereas p.Glu365Lys (E326K) and p.Thr408Met (T369M) are classified as PD risk variants. In particular, the variants E326K and T369M are common in Europeans and increase the risk of PD by a factor of about 2 in the heterozygous state [ [1]
]. A recent genetic screening study of 1360 participants identified 8.5% of PD patients to carry heterozygous GBA variants of all kinds (pathogenic or likely pathogenic for GD or significantly enriched in PD patients vs. controls; in the following collectively referred to as GBA-PD), confirming E326K (35/109; 32%) and T369M (32/109; 29%) to be the most frequent [ [2]
].