{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T10:24:00Z","timestamp":1787739840924,"version":"build-2784847793"},"posted":{"date-parts":[[2026,6,4]]},"group-title":"Genetic and Genomic Medicine","reference-count":71,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:00:00Z","timestamp":1780531200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["MH124873"],"award-info":[{"award-number":["MH124873"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["MH124871"],"award-info":[{"award-number":["MH124871"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["226770\/Z\/22\/Z"],"award-info":[{"award-number":["226770\/Z\/22\/Z"]}],"id":[{"id":"https:\/\/ror.org\/029chgv08","id-type":"ROR","asserted-by":"publisher"}]},{"award":["222811\/Z\/21\/Z"],"award-info":[{"award-number":["222811\/Z\/21\/Z"]}],"id":[{"id":"https:\/\/ror.org\/029chgv08","id-type":"ROR","asserted-by":"publisher"}]},{"award":["202408060066"],"award-info":[{"award-number":["202408060066"]}],"id":[{"id":"https:\/\/ror.org\/04atp4p48","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Antidepressants are widely prescribed for major depressive disorder, yet only one-third of patients achieve remission after initial treatment. Previous genome-wide association studies (GWAS) of clinically assessed antidepressant response combined multiple antidepressant classes, potentially obscuring class-specific effects. This study focused on selective serotonin reuptake inhibitors (SSRIs), often first-line due to better tolerability. Data from 15 cohorts across four ancestries were integrated: European (N = 3887; 11 studies), East Asian (N = 1068; 4), African (N = 277; 1), and Admixed American (N = 250; 1). GWAS of non-remission and percentage improvement were conducted within cohorts, followed by ancestry-specific meta-analyses and trans-ancestry meta-regression. Single nucleotide polymorphism (SNP)-based heritability was estimated in European samples. Polygenic scores were used for leave-one-out prediction and to assess shared genetic architecture with psychiatric traits. Gene-level and gene-set enrichment analyses were also performed. No genome-wide significant variants were identified for either outcome in any ancestry-specific or trans-ancestry analyses. However, trans-ancestry meta-regression yielded eight independent loci with suggestive associations (p &lt; 1 \u00d7 10\n                  <jats:sup>\u22125<\/jats:sup>\n                  ) for non-remission and 17 for percentage improvement. Gene-set analyses revealed nominal enrichment of the serotonergic synapse pathway for non-remission. SNP-based heritability estimates were not significantly different from zero for either outcome. Better SSRI response was nominally associated with lower genetic predisposition to major depressive disorder, post-traumatic stress disorder, and schizophrenia. This study represents the largest trans-ancestry GWAS of SSRI response, highlighting emerging biological signals. Limited power emphasises the need for larger and ancestrally diverse cohorts to better characterise the genetic architecture of antidepressant response.\n                <\/jats:p>","DOI":"10.64898\/2026.06.03.26354703","type":"posted-content","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:05:41Z","timestamp":1780617941000},"source":"Crossref","is-referenced-by-count":1,"title":["Trans-ancestry genome-wide association meta-analysis of antidepressant response to selective serotonin reuptake inhibitors in clinical studies of depression"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-2144-5418","authenticated-orcid":false,"given":"Ke","family":"Hu","sequence":"first","affiliation":[{"name":"Social, Genetic and Developmental Psychiatry Centre, King\u2019s College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3219-8942","authenticated-orcid":false,"given":"Chris Wai 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