Second hit rare genetic variants in families with seemingly GBA gene associated Parkinson’s disease

In this study, we explored the possibility that rare variation in the genetic background may be an additional risk factor for Parkinson's Disease (PD) in families segregating pathogenic GBA gene variants. We performed whole-genome sequencing, rare variant filtering, segregation analysis and functional validation of PD cosegregating rare genetic variation in two families segregating PD associated GBA variants c.115+1G>A (ClinVar ID: 93445, ) and p.L444P (ClinVar ID: 4288) respectively. We found rare genetic variation in the HSP70 co-chaperone DnaJ homolog subfamily B member 6 (DNAJB6) and lysosomal protein prosaposin (PSAP) as additional factors possibly influencing PD risk in the two families.EGA study EGAS00001004777