{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T02:16:18Z","timestamp":1790820978879,"version":"4.1.0"},"reference-count":39,"publisher":"Royal College of Psychiatrists","issue":"2","license":[{"start":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T00:00:00Z","timestamp":1736812800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0"}],"funder":[{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["1\/3 Psychiatric GWAS Consortium: Advancing Discove"],"award-info":[{"award-number":["1\/3 Psychiatric GWAS Consortium: Advancing Discove"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["1R01MH124873-01 (to SR)"],"award-info":[{"award-number":["1R01MH124873-01 (to SR)"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["R00MH116115 (to LMOL)"],"award-info":[{"award-number":["R00MH116115 (to LMOL)"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["Br J Psychiatry"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:sec id=\"S0007125024001259_sec_a1\"><jats:title>Background<\/jats:title><jats:p>Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).<\/jats:p><\/jats:sec><jats:sec id=\"S0007125024001259_sec_a2\"><jats:title>Aims<\/jats:title><jats:p>We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.<\/jats:p><\/jats:sec><jats:sec id=\"S0007125024001259_sec_a3\" sec-type=\"methods\"><jats:title>Method<\/jats:title><jats:p>Based on individual genotypes from case\u2013control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case\u2013case\u2013control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.<\/jats:p><\/jats:sec><jats:sec id=\"S0007125024001259_sec_a4\" sec-type=\"results\"><jats:title>Results<\/jats:title><jats:p>Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, <jats:italic>N<\/jats:italic> = 25 966). We observe strong genetic correlation between our case\u2013case GWAS and that of case\u2013control BPD.<\/jats:p><\/jats:sec><jats:sec id=\"S0007125024001259_sec_a5\" sec-type=\"conclusions\"><jats:title>Conclusions<\/jats:title><jats:p>We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.<\/jats:p><\/jats:sec>","DOI":"10.1192\/bjp.2024.125","type":"journal-article","created":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T06:16:16Z","timestamp":1736835376000},"page":"79-90","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":6,"title":["Identifying genetic differences between bipolar disorder and major depression through multiple genome-wide association analyses"],"prefix":"10.1192","volume":"226","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9516-6158","authenticated-orcid":false,"given":"Georgia","family":"Panagiotaropoulou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kajsa-Lotta Georgii","family":"Hellberg","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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