Analysis of Y Chromosome Haplogroups in Parkinson's Disease

Parkinsons disease is a complex neurodegenerative disorder that is about 1.5 times more prevalent in males than females. Extensive work has been done to identify the genetic risk factors behind Parkinsons disease on autosomes and more recently on chromosome X, but work remains to be done on the male specific Y chromosome. In an effort to explore the role of the Y chromosome in Parkinsons disease we analyzed whole genome sequencing data from the Accelerating Medicines Partnership - Parkinsons disease initiative (1,466 cases and 1,664 controls), genotype data from NeuroX (3,491 cases and 3,232 controls) and genotype data from UKBiobank (182,517 controls, 1,892 cases, and 3,783 proxy cases) all consisting of male European ancestry samples. We classified sample Y chromosomes by haplogroup using three different tools for comparison (Snappy, Yhaplo, Y-LineageTracker), and meta-analyzed this data to identify haplogroups associated with Parkinsons disease. This was followed up with a Y chromosome association study to identify specific variants associated with disease. We also analyzed blood based RNASeq data obtained from the Accelerating Medicines Partnership - Parkinsons disease initiative (1,020 samples) and RNASeq data obtained from the North American Brain Expression Consortium (171 samples) to identify Y chromosome genes differentially expressed in cases, controls, specific haplogroups, and specific tissues. RNASeq analyses suggest Y chromosome gene expression differs between brain and blood tissues but does not differ significantly in cases, controls or specific haplogroups. Overall, we did not find any strong associations between Y chromosome genetics and Parkinsons disease, suggesting the explanation for increased prevalence in males may lie elsewhere.