Association Analysis of Essential Tremor-Associated Genetic Variants in Sporadic Late-Onset Parkinson’s Disease

Abstract

Background: Parkinson's disease (PD) and Essential tremor (ET) are the two most common tremor diseases with recognized genetic pathogenesis. The overlapping clinical features suggest they may share genetic predispositions. Our previous study systematically investigated the association between rare coding variants in ET-associated genes and earlyonset PD (EOPD), and found the suggestive association between teneurin transmembrane protein 4 (TENM4) and EOPD. In the current research, we explored the potential genetic interplay between ET-associated genetic loci/genes and sporadic late-onset PD (LOPD). Methods:We performed whole-genome sequencing in the 1962 sporadic LOPD cases and 1279 controls from mainland China. We first used logistic regression analysis to test the top 16 SNPs identified by the ET genome-wide association study for the association between ET and LOPD. Then we applied the optimized sequence kernel association testing to explore the rare variant burden of 33 ET-associated genes in this cohort. Results:We did not observe a significant association between the included SNPs with LOPD. We also did not discover a significant burden of rare deleterious variants of ETassociated genes in association with LOPD risk. Conclusion:Our results do not support the role of ET-associated genetic loci and variants in LOPD. Highlights1. 1962 cases and 1279 controls were recruited to study the potential genetic interplay between ET-associated genetic loci/variants and sporadic LOPD. 2. No significant association between the ET-associated SNPs and LOPD were observed. 3. No significant burden of rare deleterious variants of ET-associated gene in LOPD risk were found.