Approved Research

A Phenome-wide Association and Mendelian Randomization Study for Parkinson's disease

First Affiliated Hospital of Zhengzhou University

Lay summary

The aim of this study was to systematically screen and validate a wide range of potential risk factors for Parkinson's disease (PD). Current studies have found that the incidence of PD is closely related to many factors, among which genetic factors play an important role. Large-scale Genome wide association study (GWAS) analysis further confirmed the role of gene variation in PD incidence. However, current studies mainly discuss the relationship between PD and risk factors by setting risk factors, and many risk factors are still ignored or unknown. The phenome-wide association study (PheWAS) are hypothesis-free analyses that examine genetic associations of a wide range of factors with disease. In view of the fact that genetic association can be used as a tool to identify risk factors for PD, this study intends to apply the polygenic risk score (PRS) of PD to represent the risk of PD, which can systematically screen a wide range of established and unknown non-genetic factors associated with PD. On this basis, two-sample Mendelian randomization and brain structures association analysis were used to further evaluate the potential causal relationship between the identified factors and PD and explore the potential biological mechanism of PD-PRS and PD-related factors. During this study, which is expected to be completed within 12 months, a comprehensive and rigorous assessment of the association between a wide range of risk factors and PD will be conducted. The systematic integration of genetic, clinical and neuroimaging information will help to identify risk factors and prevention goals for PD.

Considerable uncertainty remains regarding the association of multiple risk factors with brain aging related disorders(such as neurodegenerative diseases, stroke, neuro-psychiatric disorders, insomnia, headache, etc.). And further study on the risk factors, endophenotype and genotype interaction of brain aging-related diseases.