GBA1 and Gaucher disease: In the heterozygous state, however, the same pathogenic variants are strong risk factors for PD, yet without sufficient penetrance to cause a Mendelian inheritance pattern.59 Different GBA mutations show a spectrum of severity with respect to impact on enzyme activity and effect on PD susceptibility, ranging from around tenfold increased risk for carriers of L444P60 to less than twofold in the low-frequency variant E326K,61,62 which does not cause Gaucher’s disease in the homozygous state.