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Psychiatric genome-wide association studies (GWAS) have identified hundreds of genome-wide significant (GWS) loci that have rapidly advanced our understanding of disease etiology. However, whether these results can be leveraged to improve clinical treatment for specific psychiatric disorders remains poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this proof-of-principal evaluation of GWAS clinical utility, we test whether the targets of drugs used to treat Attention Deficit Hyperactivity Disorder (ADHD), Bipolar Disorder (BiP), Generalized Anxiety Disorder (GAD), Major Depressive Disorder (MDD), Post-Traumatic Stress Disorder (PTSD), Schizophrenia (SCZ), Substance Use Disorders (SUDs), and insomnia (INS), are enriched for GWAS meta-analysis findings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The genes coding for treatment targets of medications used to SCZ, BiP, MDD, and SUDs (but not ADHD, PTSD, GAD, or INSOM) are enriched for GWS loci identified in their respective GWAS (ORs: 2.78-27.63; all ps &lt;1.15e-3). Enrichment is largely driven by the presence of a GWS locus or loci within a gene coding for a drug target (i.e., proximity matching). Broadly, additional annotation (i.e., functional: Combined Annotation Dependent Depletion [CADD] scores, regulomeDB scores, eQTL, chromatin loop, and gene region; statistical: effect size of genome-wide significant SNPs; Z-score of SNPs; number of drug targets implicated by GWAS), with the exception of weighting by the largest SNP effect size, does not further improve enrichment across disorders. Evaluation of prior smaller GWAS reveal that more recent larger GWAS improve enrichment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>GWAS results may assist in the prioritization of medications for future psychopharmaceutical research.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s43856-025-00877-9","type":"journal-article","created":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T07:58:51Z","timestamp":1747382331000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Psychiatric genome-wide association study enrichment shows promise for future psychopharmaceutical discoveries"],"prefix":"10.1038","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8002-7267","authenticated-orcid":false,"given":"Alexander S.","family":"Hatoum","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron J.","family":"Gorelik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Blaydon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spencer B.","family":"Huggett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingying","family":"Chi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6659-357X","authenticated-orcid":false,"given":"David A. 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Huggett is an employee of HiFi Bio and sole owner of SYNAPZE LLC. He was not employed by HiFiBiO Therapeutics or SYNAPZE LLC during his work on this project. HiFiBiO Therapeutics had no role in the analysis, and no technology or supplies from their company were used herein. Alexander S. Hatoum and Spencer B. Huggett are listed as inventors on two preliminary patents related to these analyses, T-020521\u2014Treatments for multi-drug or broad addiction liability, and T-020507 Multi-omics algorithm for testing neurological and psychiatric pharmaceutical efficacy. All other authors declare no competing interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Spencer B. Huggett is the owner of Synapze LLC. Synapze LLC had no role in the analysis, and no technology or supplies from their companies were used herein. Alexander S. Hatoum and Spencer B. Huggett are listed as inventors on two preliminary patents related to these analyses, T-020521\u2014\u201cTreatments for multi-drug or broad addiction liability\u201d, and T-020507 \u201cMulti-omics algorithm for testing neurological and psychiatric pharmaceutical efficacy\u201d.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Disclosure"}}],"article-number":"176"}}