Study Rationale: Genetic variants in TMEM175 are amongst the top 5 strongest genetic risk variants in Parkinson’s disease (PD), with one variant increasing risk for the disease, and one variant reducing risk. However, not much is known about other genetic variants in TMEM175, and it is also unclear whether the known variants in TMEM175 have effects on different symptoms and biomarkers of PD. In this study, we will address this gap.
Hypothesis: We hypothesize that there are additional variants in TMEM175 that affect the risk of PD, and that variants in this gene may be associated with different symptoms and biomarkers of PD.
Study Design: We will use the world’s largest cohorts of individuals with PD from different sources, such as the Global Parkinson’s Genetics Program (GP2), UK Biobank, Parkinson's Progression Markers Initiative (PPMI) and others, to perform a comprehensive genetic and clinical analysis of individuals with and without variants in TMEM175.
Impact on Diagnosis/Treatment of Parkinson’s disease: TMEM175 is an attractive target for therapeutic development, given its biological role. Characterizing it as we suggest will advance those clinical efforts to develop treatments targeting TMEM175.
Next Steps for Development: The results of this study will inform researchers and industry on which individuals to prioritize with potential treatments for TMEM175 and which biomarkers to explore as outcomes for future trials. It will also inform basic researchers who are interested in better understanding the biological mechanism behind the association between TMEM175 and PD.