The role of RHOT1 and RHOT2 genetic variation on Parkinson disease risk and onset

Genetic variation within the mitochondrial pathway contributes to the risk of Parkinson's disease (PD). Recent genetic analyses have investigated the association between the RHOT1 and RHOT2 genes and PD etiology. Furthermore, 4 mutations in the RHOT1 gene (p.R272Q, p.R450C, p.T351A, p.T610A) have been reported to be potentially associated with disease risk. As part of the International Parkinson Disease Genomics Consortium efforts to evaluate reported PD risk factors, we assessed the role of common and low frequency variants in both RHOT1 and also RHOT2 according to the high degree of homology in their amino acid sequences. Utilizing large-scale genotyping and whole-genome sequencing data from the International Parkinson Disease Genomics Consortium and the Accelerating Medicines Partnership - Parkinson Disease initiative, our analyses did not identify evidence to support the hypothesis that RHOT1 and RHOT2 are disease causing or modifying genes for PD risk or age at onset. (C) 2020 Elsevier Inc. All rights reserved.

Automated summary

Genetic variation within the mitochondrial pathway is considered to contribute to the risk of Parkinson's disease, with recent studies investigating the association between the RHOT1 and RHOT2 genes and PD etiology. However, analyses using large-scale genotyping and whole-genome sequencing data did not find evidence to support a role for RHOT1 and RHOT2 as disease-causing or modifying genes for PD risk or age at onset.