Genetic Analysis of the
SLC38A6
Gene in Chinese Patients with Essential Tremor: Not Causative, But Rather an Additional Susceptibility Gene?
Hongwei Wu, Nan Jin, Xiaosheng Zheng, Xinhui Chen, Wenxuan Bi, Siyu Xie, Jiawen Chen, Weili Luo, Jiaxiang Li, Dehao Yang, You Chen, Si Chen, Lixia Gao, Zhidong Cen, Wei Luo Abstract
Background
A recent study implicated rare SLC38A6 variants in Han Chinese cases of essential tremor (ET).
Objectives
To validate the association between SLC38A6 and ET in an independent cohort via gene‐level burden analysis and family co‐segregation.
Methods
We sequenced all coding exons and splice sites of SLC38A6 in 724 Han Chinese ET patients and 606 controls, performing gene‐level burden tests and co‐segregation analysis.
Results
Eleven rare variants were identified. The most recurrent variant, c.323A>T (p.Y108F), was enriched in cases (3.45% vs. 1.16%; odds ratio [OR] 3.06, 95% confidence interval [95% CI] 1.31–7.13, P = 0.0065). Gene‐level analysis showed significantly more rare‐variant carriers in cases than in controls (7.73% vs. 3.63%; OR 2.23, 95% CI 1.34–3.69, P = 0.0015), confirmed by sequence kernel association test (SKAT) ( P = 0.0257). Six of 12 families showed co‐segregation of c.323A>T (p.Y108F), c.719C>A (p.P240Q), or c.752A>G (p.Y251C) with ET.
Conclusions
These findings support SLC38A6 as a candidate susceptibility gene for ET in Han Chinese. © 2026 International Parkinson and Movement Disorder Society.