Gene discovery and pleiotropic architecture of multidimensional pain in a genome-wide association study of >1.2 million individuals.

A meta-analytic genome-wide association study of multidimensional pain in 1,235,695 European-ancestry individuals identified 343 independent loci, including 92 new pain associations.

• Why it matters: Chronic pain is common, but its genetic architecture and how it relates to other conditions remain incompletely mapped, especially across multiple pain dimensions.
• What they did: The study combined three biobanks for a meta-analytic GWAS of multidimensional pain, then used sex-specific analyses, multi-omic gene prioritization, Mendelian randomization, and brain-imaging pleiotropy tests.
• The result: Multi-omic prioritization implicated 490 genes via brain- and blood-specific regulation, and Mendelian randomization linked multidimensional pain to psychiatric disorders, substance use disorders, and C-reactive protein levels.

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