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We investigated clinical correlates of second-generation antipsychotic (SGA) treatment response and conducted the first genome-wide association study (GWAS), including exploratory polygenic scores (PGS), of SGA pharmacogenomic treatment response in BD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Treatment response was quantified using the Alda scale, and GWAS was performed using Alda-A score, controlling for sex, genotyping batch, and the genomic principal components.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The cohort included 2,159 adults with BD (1,416 BD-I, 691 BD-II, 51 schizoaffective BD), mean age 41.8 years, 62% female, 84% white, and 14% Hispanic. Nearly half (48%) were treated with SGAs. Current SGA users were younger (41.2\u2009\u00b1\u200914.7 vs. 42.5\u2009\u00b1\u200915.3 years,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.040), more likely to be Hispanic (14% vs. 11%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.047), had a higher body mass index (BMI; 30.4\u2009\u00b1\u20097.6 vs. 29.5\u2009\u00b1\u20097.1\u00a0kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      ,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.005). Lifetime comorbidity patterns for current SGA users include higher rates of manic psychosis (29% vs. 17%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and eating disorders \u2014 Anorexia Nervosa (7% vs. 4%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.003), Bulimia Nervosa (7% vs. 4%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.003), and Binge Eating Disorder (14% vs. 11%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.030). We detected a genome-wide significant association between SGA Alda-A scores and\n                      <jats:italic>GAS7<\/jats:italic>\n                      variants (top variant: rs202127418,\n                      <jats:italic>\u03b2<\/jats:italic>\n                      =-2.998,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20094.96E-08). However, SGA response was not significantly associated with PGS for schizophrenia, BD, and major depression (FDR\u2009&gt;\u20090.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      SGAs are frequently utilized as mood stabilizers in patients with BD and are associated with manic psychosis and eating disorders.\n                      <jats:italic>GAS7<\/jats:italic>\n                      variants may predict SGA response, but larger, more diverse cohorts are needed for validation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40345-025-00405-7","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T10:28:55Z","timestamp":1765189735000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Antipsychotic use in bipolar disorder: clinical and genomic correlates\u2013 a Mayo clinic bipolar disorder biobank study"],"prefix":"10.1186","volume":"14","author":[{"given":"Balwinder","family":"Singh","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ada Man-Choi","family":"Ho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brandon J.","family":"Coombes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisco","family":"Romo-Nava","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David J.","family":"Bond","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marin","family":"Veldic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard S.","family":"Pendegraft","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony","family":"Batzler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfredo B.","family":"Cuellar-Barboza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel","family":"Gardea-Res\u00e9ndez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel L.","family":"Prieto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aysegul","family":"Ozerdem","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan L.","family":"McElroy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanna M.","family":"Biernacka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark A.","family":"Frye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,12,8]]},"reference":[{"key":"405_CR1","doi-asserted-by":"publisher","first-page":"2776","DOI":"10.1093\/bioinformatics\/btx299","volume":"33","author":"G Abraham","year":"2017","unstructured":"Abraham G, Qiu Y, Inouye M. 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Written informed consent was obtained from all participants.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"MAF received grant support from Assurex Health and Mayo Foundation, received CME travel and honoraria from Carnot Laboratories and American Physician Institute, and has Financial Interest\/Stock ownership\/Royalties from Chymia LLC. SLM is a consultant to, or member of the scientific advisory boards of, in the past year: Axsome, Idorsia, Levo, Kallyope, MycoMedica, Novo Nordisk, Otsuka, and Soleno. SLM is presently or has been in the past year a principal or co-investigator on research studies sponsored by: Axsome, Idorsia, Marriott Foundation, National Institute of Mental Health, Novo Nordisk, and Otsuka. Patents: SLM 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. FRN is supported in part by NIMH grants K23MH120503 and 1R61MH133770-01A1; is the inventor on a U.S. Patent and Trademark Office patent # 10,857,356. MGR receives research support from Consejo Nacional de Humanidades, Ciencias y Tecnolog\u00edas (CONAHCYT) in Mexico. BS reports research grant support from the Mayo Clinic, the National Network of Depression Centers, and Breakthrough Discoveries for Thriving with Bipolar Disorder (BD2). He is a KL2 Mentored Career Development Program scholar, supported by CTSA Grant Number KL2 TR002379 from the National Center for Advancing Translational Science (NCATS). He has received honoraria (to Mayo Clinic) from Elsevier for editing a Clinical Overview on Treatment-Resistant Depression. The rest of the co-authors have no conflict of interest to declare.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1"}}