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We investigated the polygenic overlap between MOOD and psychiatric disorders beyond genetic correlation to better characterize putative shared genetic determinants. GWAS summary statistics for schizophrenia (SCZ,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009105,318), bipolar disorder (BIP,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009413,466), DEP (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009450,619), attention\u2010deficit hyperactivity disorder (ADHD,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200953,293), and MOOD (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009363,705) were analyzed using the bivariate causal mixture model and conjunctional false discovery rate methods. MOOD correlated positively with all psychiatric disorders, but with wide variation in strength (\n                    <jats:italic>r<\/jats:italic>\n                    <jats:sub>g<\/jats:sub>\n                    \u2009=\u20090.10\u20130.62). Of 10.4\u00a0K genomic variants influencing MOOD, 4\u00a0K\u20139.4\u00a0K influenced psychiatric disorders. Furthermore, MOOD was jointly associated with DEP at 163 loci, SCZ at 110, BIP at 60 and ADHD at 25. Fifty\u2010three jointly associated loci were overlapping across two or more disorders, seven of which had discordant effect directions on psychiatric disorders. Genes mapped to loci associated with MOOD and all four disorders were enriched in a single gene\u2010set, \u201csynapse organization.\u201d The extensive polygenic overlap indicates shared molecular underpinnings across MOOD and psychiatric disorders. However, distinct patterns of genetic correlation and effect directions may relate to differences in the core clinical features of each disorder.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.b.32907","type":"journal-article","created":{"date-parts":[[2022,7,16]],"date-time":"2022-07-16T02:45:45Z","timestamp":1657939545000},"page":"207-218","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["The shared genetic basis of mood instability and psychiatric disorders: A cross\u2010trait genome\u2010wide association analysis"],"prefix":"10.1002","volume":"189","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1666-4701","authenticated-orcid":false,"given":"Guy","family":"Hindley","sequence":"first","affiliation":[{"name":"NORMENT Centre, Institute of Clinical Medicine University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital  Oslo Norway"},{"name":"Psychosis Studies Institute of 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