Lack of evidence for association of UQCRC1 with autosomal dominant Parkinson's disease in Caucasian families

See Cerri and Valente (doi:10.1093/brain/awaa324) for a scientific commentary on this article. Ubiquinol-cytochrome c reductase core protein I (UQCRC1) is a complex III core protein of the mitochondrial electron transport chain. Lin et al. identify rare missense mutations in mitochondrial UQCRC1 that segregate with Parkinson’s disease, and show that they are functionally pathogenic.

Recently, a novel variant p.Y314S in UQCRC1 has been implicated as pathogenic in Parkinson's disease (PD). In the present study, we aimed to examine the association of UQCRC1 with PD in large cohorts of European origin. We examined common and rare genetic variation in UQCRC1 using genome-wide association study data from the International Parkinson Disease Genomics Consortium, including 14,671 cases and 17,667 controls, and whole-genome sequencing data from the Accelerating Medicines Partnership-Parkinson's disease initiative, including 1647 patients with PD and 1050 controls. No common variants were consistently associated with PD, and a variety of burden analyses did not reveal an association between rare variants in UQCRC1 and PD. Therefore, our results do not support a major role for UQCRC1 in PD in the European population, and additional studies in other populations are warranted.