{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T16:18:37Z","timestamp":1777997917597,"version":"3.51.4"},"reference-count":83,"publisher":"S. Karger AG","issue":"1 - 4","license":[{"start":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T00:00:00Z","timestamp":1772668800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T00:00:00Z","timestamp":1772668800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Complex Psychiatry"],"abstract":"<jats:p>Introduction: Somatoform traits (e.g., health anxiety, somatic preoccupation, and bodily distress symptoms) are prevalent and pose challenges to clinical practice. Understanding their genetic basis could improve diagnostic and therapeutic approaches. Methods: Using available summary statistics, we conducted a multivariate genome-wide association study (GWAS) and multi-omic analysis of four somatoform traits \u2013 fatigue, irritable bowel syndrome, pain intensity, and health satisfaction \u2013 in 799,429 individuals genetically similar to European reference panels. Results: The GWAS identified 134 loci associated with a somatoform common factor, including 44 loci not significant in the input GWAS and 8 novel loci for somatoform traits. Novel loci were mechanistically informative, mapping to the DNM1 gene and the protocadherin gene cluster (PCDHA1-4), which are involved in nociceptor sensitization and synaptogenesis, respectively. Gene-property analyses highlighted an enrichment of genes involved in synaptic transmission and enriched expression in 11 brain tissues and the pituitary. Across two brain transcriptomic datasets, we identified 16 high-confidence genes whose expression in enriched tissues was associated with somatoform traits. There was substantial polygenic overlap (76\u201383%) between the somatoform and externalizing, internalizing, and general psychopathology factors. Somatoform polygenic scores were associated with obesity, type 2 diabetes, and tobacco use disorder in independent biobanks. Drug repurposing analyses suggested potential therapeutic targets, including MEK inhibitors, while Mendelian randomization analyses indicated potentially protective effects of gut microbiota. Discussion: Consistent with emerging medical and genetic knowledge, somatoform traits have a shared etiology and considerable polygenic overlap with psychopathology. The biological insights from drug repurposing and Mendelian randomization analyses could provide promising avenues for treatment development.<\/jats:p>","DOI":"10.1159\/000551114","type":"journal-article","created":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T17:01:04Z","timestamp":1772730064000},"page":"27-39","source":"Crossref","is-referenced-by-count":0,"title":["Multivariate, Multi-Omic Analysis in 799,429 Individuals Identifies 134 Loci Associated with Somatoform Traits"],"prefix":"10.1159","volume":"12","author":[{"given":"Christal N.","family":"Davis","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylvanus","family":"Toikumo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander 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