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Transcriptome-wide association study identifies novel candidate susceptibility genes for migraine
Travis J Meyers1, Jie Yin1, Victor A Herrera1
1Division of Research, Kaiser Permanente Northern California, Oakland, CA 94612, USA.
HGG Advances
|July 7, 2023
Summary
This study used transcriptome-wide association studies (TWAS) to identify novel genes linked to migraine susceptibility. It found 53 associated genes, with 10 not previously linked to migraine, highlighting roles for brain, cardiovascular, and gastrointestinal tissues.
Area of Science:
- Genetics
- Neuroscience
- Computational Biology
Background:
- Genome-wide association studies (GWAS) have identified over 130 migraine susceptibility loci, but their functional impact remains largely unknown.
- Understanding the genetic underpinnings of migraine is crucial for developing targeted therapies.
Purpose of the Study:
- To identify novel genes associated with migraine susceptibility.
- To interpret the transcriptional products of genes implicated in migraine.
- To explore the tissue-specific contributions to migraine pathogenesis.
Main Methods:
- Conducted tissue-specific and multi-tissue transcriptome-wide association studies (TWAS) using FUSION software.
- Utilized meta-analyzed GWAS summary statistics from 26,052 migraine cases and 487,214 controls (European ancestry).
- Performed colocalization analyses to assess shared genetic variants between GWAS loci and expression quantitative trait loci (eQTLs).
Main Results:
- Identified 53 genes significantly associated with migraine risk through genetically predicted gene expression.
- Discovered 10 novel migraine-associated genes not previously identified by GWAS.
- Found significant gene-tissue associations in cardiovascular (49%), brain (13%), and gastrointestinal (9%) tissues.
- Provided evidence for shared genetic variants in 40% of gene-tissue pairs through colocalization analysis.
Conclusions:
- The study reports novel genes contributing to migraine susceptibility.
- Highlights the significant roles of brain, cardiovascular, and gastrointestinal tissues in migraine.
- TWAS is a valuable approach for uncovering the functional genetic architecture of complex diseases like migraine.
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