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Genetics

GWAS and eQTL disparity

Nature Methods volume 20, page 1873 (2023)Cite this article

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Genome-wide association studies (GWAS) and expression quantitative trait loci (eQTL) mapping use conceptually similar ideas to identify genetic variants contributing to complex trait and gene expression variation, respectively. Despite the proven role of gene expression in mediating biological functions, the observed level of colocalization between GWAS hits and eQTLs shows a gap that challenges the expectation that eQTLs would account for a large proportion of GWAS hits. Intrigued by this riddle, Hakhamanesh Mostafavi, Jonathan Pritchard and their colleagues at Stanford University gave it a deep and comprehensive examination.

“This was a big, messy, complicated problem,” says Pritchard. Using data from the UK Biobank and GTEx, the team designed a pipeline to generate high-quality and comparable collections of GWAS hits and eQTLs while paying special attention to including matched control single-nucleotide polymorphisms. Their results showed notable differences in functional, regulatory and evolutionary features between these two types of variants and their closest genes, enhancing previous findings that “spread across many different papers with different methods of analysis. … I think it is hugely impactful to see all these different analyses collected together with a unified analysis approach to help us understand how systematically different these two types of signals [eQTL and GWAS] are,” says Pritchard.

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  1. Nature Methods https://www.nature.com/nmeth/

    Lin Tang

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  1. Lin Tang
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Correspondence to Lin Tang.

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Tang, L. GWAS and eQTL disparity. Nat Methods 20, 1873 (2023). https://doi.org/10.1038/s41592-023-02133-1

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