{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T21:46:38Z","timestamp":1792014398924,"version":"4.4.0"},"reference-count":112,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Psychiatry"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Twin studies reveal high genetic overlap between anxiety disorders and depression, contributing to the internalising spectrum. Some genetic specificity for fear-based anxiety disorders (fear), distinct from general anxiety and depression (distress), has also emerged. Limited datasets with detailed phenotyping across anxiety disorders have restricted most genome-wide association studies (GWAS) to \u201cany anxiety diagnosis\u201d. Additional genome-wide evidence to discern genetic differences between fear and distress is required. We conducted GWAS meta-analyses of fear (panic, agoraphobia, specific phobia, social anxiety disorder) and generalised anxiety disorder (GAD), measured using brief single-item and detailed symptom-based diagnoses from three datasets. We explored two control group criteria: phenotype-specific (fear\/GAD) or broader anxiety\/depression screening. We identified one independent genome-wide significant locus and three gene-level associations with fear (up to 35,523 N\n                    <jats:sub>cases<\/jats:sub>\n                    ; 157,447 N\n                    <jats:sub>controls<\/jats:sub>\n                    ). Four genome-wide significant loci and three gene-level associations were identified for GAD (up to 60,879 N\n                    <jats:sub>cases<\/jats:sub>\n                    ; 117,064 N\n                    <jats:sub>controls<\/jats:sub>\n                    ). The genetic correlation between fear and GAD was significantly different from unity only when excluding a depression-enriched dataset and using phenotype-specific control screening (r\n                    <jats:sub>g<\/jats:sub>\n                    = 0.87; P\u2009=\u20099.32\u2009\u00d7\u200910\n                    <jats:sup>\u22123<\/jats:sup>\n                    ). Most complex traits had statistically similar genetic correlations with fear and GAD, including depression. Exceptions included general cognitive ability, educational attainment, and coronary artery disease, showing statistically stronger genetic correlations with fear than GAD, while bipolar disorder type I, anorexia nervosa, and neuroticism displayed the opposite pattern. Our findings partially support a distress-fear genetic distinction, but show stronger evidence for an overarching genetic liability to internalising psychopathology driving comorbidity across anxiety disorders and depression.\n                  <\/jats:p>","DOI":"10.1038\/s41380-026-03677-2","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T10:47:02Z","timestamp":1782730022000},"page":"6224-6237","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genome-wide genetic overlap between fear-based disorders and generalised anxiety disorder"],"prefix":"10.1038","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7869-3754","authenticated-orcid":false,"given":"Abigail R.","family":"ter Kuile","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\/0000-0002-5610-033X","authenticated-orcid":false,"given":"Sang Hyuck","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5322-6252","authenticated-orcid":false,"given":"Genevi\u00e8ve","family":"Morneau-Vaillancourt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7619-349X","authenticated-orcid":false,"given":"Megan","family":"Skelton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6759-0944","authenticated-orcid":false,"given":"Jonathan R. 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AMM has received research support from Eli Lilly, Janssen and The Sackler Trust. AMM has also received speaker fees from Illumina and Janssen. All other authors have nothing to disclose.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"The London Fulham Research Ethics Committee approved the GLAD Study (21st August 2018; REC reference: 18\/LO\/1218) and EDGI UK (29th July, 2019; REC reference: 19\/LO\/1254). Ethical approval for the COPING Study was granted following a full review by the South West Central Bristol Research Ethics Committee (REC reference: 20\/SW\/0078) on 27th April 2020. The AGDS and QSkin cohorts were reviewed and approved by the QIMR Berghofer Medical Research Institute\u2019s Human Research Ethics Committee. Analyses in the UK Biobank were performed under UK Biobank Project Application 82087. The UK Biobank has ethical approval from the North West Multi-centre Research Ethics Committee (MREC) as a Research Tissue Bank (RTB) approval. All participants provided informed consent, and all methods were performed in accordance with the relevant guidelines and regulations.","order":2,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Ethics"}}]}}