From genetic associations to genes: methods, applications, and challenges.

Trends Genet

Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou 310024, China; School of Life Sciences, Westlake University, Hangzhou 310024, China. Electronic address:

Published: August 2024

Genome-wide association studies (GWASs) have identified numerous genetic loci associated with human traits and diseases. However, pinpointing the causal genes remains a challenge, which impedes the translation of GWAS findings into biological insights and medical applications. In this review, we provide an in-depth overview of the methods and technologies used for prioritizing genes from GWAS loci, including gene-based association tests, integrative analysis of GWAS and molecular quantitative trait loci (xQTL) data, linking GWAS variants to target genes through enhancer-gene connection maps, and network-based prioritization. We also outline strategies for generating context-dependent xQTL data and their applications in gene prioritization. We further highlight the potential of gene prioritization in drug repurposing. Lastly, we discuss future challenges and opportunities in this field.

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http://dx.doi.org/10.1016/j.tig.2024.04.008DOI Listing

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