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The Mood Stabilizer Genomics (MoStGen) Consortium was established to investigate pharmacogenomic and clinical predictors of response to treatment of BD with antiepileptic drug mood stabilizers (AMS). Here we present the first pharmacogenomic analyses of AMS treatment outcomes based on MoStGen Consortium data, including 917 individuals across contributing sites. We performed genome-wide association analyses in subcohorts followed by meta-analyses, with AMS treatment response measured quantitatively using the Alda scale. Medication-stratified analyses were performed for valproic acid (VPA) and lamotrigine (LTG) treatment response. Additionally, polygenic score (PGS) analyses were used to evaluate the overall genetic contribution to AMS response across cohorts and to test whether genetic liability for various neuropsychiatric illnesses impacts AMS response. We detected genome-wide significant associations with LTG treatment response for SNPs in the gene\n                    <jats:italic>ROBO2<\/jats:italic>\n                    (top SNP: rs985123,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20091.9E-10) and for\n                    <jats:italic>POLR1E<\/jats:italic>\n                    at the gene-level (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20092.53E-06). No significant associations were found for overall AMS or VPA treatment response. Leave-one-out PGS analyses provided significant evidence for a polygenic signal for AMS treatment response. Furthermore, the epilepsy PGS was nominally significantly associated with AMS response (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.024), suggesting higher genetic liability to epilepsy predicts a better response to treatment with AMS. These findings provide insights into the genetic contribution to AMS treatment outcomes, and in particular LTG response, and may contribute to the development of more precise treatments for BD.\n                  <\/jats:p>","DOI":"10.1038\/s41380-026-03478-7","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T08:43:18Z","timestamp":1771490598000},"page":"3587-3594","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pharmacogenomics of antiepileptic drug mood stabilizer treatment response in bipolar disorder: A MoStGen Consortium study"],"prefix":"10.1038","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4989-8782","authenticated-orcid":false,"given":"Ada 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SLM is a consultant to, or member of the scientific advisory boards, in the past year: Axsome, Idorsia, Kallyope, Levo. Novo Nordisk, and Soleno; and is presently or has been in the past year a principal or co-investigator on research studies sponsored by: Axsome and Marriott Foundation. She is also inventor on United States Patent No. 6,323,236 B2, Use of Sulfamate Derivatives for Treating Impulse Control Disorders, and, along with the patent\u2019s assignee, University of Cincinnati, Cincinnati, OH, has received payments from Johnson & Johnson Pharmaceutical Research & Development, L.L.C., which has exclusive rights under the patent. All other authors have no conflicts of interest in relation to this work to declare.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}