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Brain Disease Driver Candidates Uncovered in Expression, Regulatory Study

In Nature Genetics, researchers from centers in the Netherlands, the UK, and the US present brain trait- and disease-related findings gleaned from their MetaBrain resource, a collection of more than 8,600 RNA-sequenced samples from seven brain regions. With the help of corresponding genotyping profiles, the team performed a series of expression quantitative trait loci (eQTLs) meta-analyses, uncovering nearly 16,200 locally acting cis-eQTLs with tissue-specific activity in the brain's cortex, more than 3,500 brain cell type-specific cis-eQTLs, thousands of "interaction" eQTLs, and 737 trans-eQTLs with more distant effects. Together with co-regulation network clues and risk variant data from prior past genome-wide association studies, such eQTLs helped the authors narrow in on hundreds of genes with apparent ties to brain traits or conditions. "Our dataset can be utilized to disambiguate GWAS loci, point to causal pathways, and prioritize targets for drug discovery," they explain. "We expect that through future integration with single-cell eQTL studies that have higher resolution but still lower power, our results will help to pinpoint transcriptional effects in specific brain cell types for many disease-associated genetic variants."

The Scan

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