Genome-wide analysis identifies non-reference transposable element polymorphisms associated with Parkinson’s disease

Abstract

Parkinson’s disease (PD) is a common neurodegenerative disease that primarily affects the elderly, significantly impacting patients’ health and quality of life. While most genetic studies on PD have focused on single nucleotide polymorphisms, the effects of other forms of genomic variation in PD are yet to be fully elucidated. Transposable elements (TEs) are one of the main sources of human genome structural variation, with known associations with many human diseases. However, their potential connection to PD remains unclear. In this study, we investigated non-reference TE polymorphisms in three independent PD cohorts and explored their associations with both PD risk and progression. Our findings revealed that one non-reference TE is associated with the risk of PD, while two TEs are associated with disease progression. Furthermore, through expression quantitative trait locus (eQTL) analysis, we identified 18 cis TE-eQTLs in an interaction model and 290 cis TE-eQTLs in a non-interaction model. Several non-reference TE polymorphisms are correlated with specific PD-gene expression patterns in trans. These results indicate the feasibility of delving into the genetics of PD through the study of complex genomic variations. Advances in genomics research have the potential to deepen our understanding of this disease and pave the way for further translational medicine research in PD.