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Here we performed a genome-wide association meta-analysis of generalized anxiety symptom severity in 693,869 individuals of European ancestry from 14 cohorts. We identified 80 independent genome-wide significant variants within 74 loci, 39 of which were newly associated with anxiety. SNP-based heritability was 5.9% (posterior s.d.\u2009=\u20090.15%). Polygenic scores were significantly associated with anxiety symptom severity and disorder in European, African and South Asian ancestry samples (\n                    <jats:italic>R<\/jats:italic>\n                    <jats:sup>2<\/jats:sup>\n                    \u2009=\u20091.2\u20132.9%). Significant genetic correlations (\n                    <jats:italic>r<\/jats:italic>\n                    <jats:sub>g<\/jats:sub>\n                    ) were estimated with mental and physical health traits, including case\u2013control anxiety, neuroticism and depression (\n                    <jats:italic>r<\/jats:italic>\n                    <jats:sub>g<\/jats:sub>\n                    \u2009=\u20090.71\u20130.85), irritable bowel syndrome (\n                    <jats:italic>r<\/jats:italic>\n                    <jats:sub>g<\/jats:sub>\n                    \u2009=\u20090.57), coronary artery disease, endometriosis and migraine (\n                    <jats:italic>r<\/jats:italic>\n                    <jats:sub>g<\/jats:sub>\n                    \u2009=\u20090.20\u20130.27). Gene-based and pathway analyses implicated synaptic and axonal processes, with enriched expression in the brain. These findings highlight the discovery power gained from analysing a quantitative trait rather than a case\u2013control phenotype in anxiety genetics.\n                  <\/jats:p>","DOI":"10.1038\/s41562-026-02476-7","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T09:01:39Z","timestamp":1780995699000},"page":"1594-1608","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Genome-wide meta-analysis of quantitatively measured generalized anxiety symptoms in individuals of European ancestry"],"prefix":"10.1038","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7619-349X","authenticated-orcid":false,"given":"Megan","family":"Skelton","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9050-1516","authenticated-orcid":false,"given":"Brittany L.","family":"Mitchell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9788-0478","authenticated-orcid":false,"given":"Elham","family":"Assary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danyang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5322-6252","authenticated-orcid":false,"given":"Genevieve","family":"Morneau-Vaillancourt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2487-8753","authenticated-orcid":false,"given":"Alan E.","family":"Murphy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7869-3754","authenticated-orcid":false,"given":"Abigail R.","family":"ter Kuile","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rujia","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3599-6018","authenticated-orcid":false,"given":"Mark J.","family":"Adams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9491-7797","authenticated-orcid":false,"given":"Enda M.","family":"Byrne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0119-157X","authenticated-orcid":false,"given":"Elizabeth C.","family":"Corfield","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9913-2382","authenticated-orcid":false,"given":"Poppy Z.","family":"Grimes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3123-5411","authenticated-orcid":false,"given":"Laurie J.","family":"Hannigan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihua","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5286-2014","authenticated-orcid":false,"given":"Kadri","family":"K\u00f5iv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1953-2771","authenticated-orcid":false,"given":"Alex S. 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O.A.A. served as a consultant for Precision-Health.ai and Cortechs.ai, and has received speaker\u2019s honorarium from BMS, Lundbeck, Otsuka, Sunovion, Janssen and Lilly. K.D. is a member of the Neurotorium Editorial Board of the Lundbeck Foundation and has received speaker\u2019s honoraria by Janssen Cilag GmbH, not related to the subject of this paper. I.B.H is a professor of psychiatry and the codirector of Health and Policy, Brain and Mind Centre, University of Sydney. He has led major public health and health service development in Australia, particularly focusing on early intervention for young people with depression, suicidal thoughts and behaviours and complex mood disorders. He is active in the development through codesign, implementation and continuous evaluation of new health information and personal monitoring technologies to drive highly personalized and measurement-based care. He holds a 3.2% equity share in Innowell Pty Ltd that is focused on digital transformation of mental health services. A.M.M. has received research support from Eli Lilly, Janssen and The Sackler Trust. A.M.M. has also received speaker fees from Illumina and Janssen. J.D. is a member of the board of the German Society of Biological Psychiatry and is on the scientific advisory boards of non-profit organizations and foundations. The other authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}]}}