Genome-wide association study in essential tremor identifies three new loci.

Area of Science:

• Neurogenetics
• Human Genetics

Background:

• Essential tremor is a common, highly heritable movement disorder.
• The underlying molecular genetic factors for essential tremor remain largely unknown.

Purpose of the Study:

• To identify genetic variants associated with essential tremor through a genome-wide association study (GWAS).
• To investigate the role of candidate genes in essential tremor pathogenesis.

Main Methods:

• A two-stage genome-wide association study was performed, including 2807 patients and 6441 controls of European descent.
• Significantly associated markers from the discovery stage were genotyped in a replication cohort.
• Gene expression analysis and expression quantitative trait loci (eQTL) mining were conducted for candidate genes.

Main Results:

• Two markers, rs10937625 (STK32B) and rs17590046 (PPARGC1A), were significantly associated with essential tremor after Bonferroni correction.
• Three markers in CTNNA3 were significant in the combined analysis.
• Increased STK32B expression was found in the cerebellar cortex of patients, and the protective allele of rs10937625 was associated with reduced STK32B expression in the cerebellum.

Conclusions:

• This study identifies novel genetic associations for essential tremor, implicating STK32B, PPARGC1A, and CTNNA3.
• Increased STK32B expression in the cerebellum may contribute to essential tremor development.
• Previous associations with SLC1A2 and LINGO1 were not replicated.