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We investigated the mediational pathways from family\/genetic risk for suicide attempt (FGRS<jats:sub>SA<\/jats:sub>) to suicide attempt by considering the roles of psychiatric illnesses. In a Swedish cohort, we evaluated time to suicide attempt as a function of FGRS<jats:sub>SA<\/jats:sub> and the mediational effects of alcohol use disorder, drug use disorder, attention\u2010deficit\/hyperactivity disorder, major depression, anxiety disorder, bipolar disorder, and non\u2010affective psychosis. Analyses were conducted by sex in three age periods: 15\u201325 years (<jats:italic>N<\/jats:italic><jats:sub>females<\/jats:sub>\u2009=\u2009850,278 and <jats:italic>N<\/jats:italic><jats:sub>males<\/jats:sub>\u2009=\u2009899,366), 26\u201335 years (<jats:italic>N<\/jats:italic><jats:sub>females<\/jats:sub>\u2009=\u2009800,189 and <jats:italic>N<\/jats:italic><jats:sub>males<\/jats:sub>\u2009=\u2009861,774), and 36\u201345 years (<jats:italic>N<\/jats:italic><jats:sub>females<\/jats:sub>\u2009=\u2009498,285 and <jats:italic>N<\/jats:italic><jats:sub>males<\/jats:sub>\u2009=\u2009535,831). The association between FGRS<jats:sub>SA<\/jats:sub> and suicide attempt was mediated via psychiatric disorders. The highest mediation effects were observed for alcohol use disorder in males (15\u201325\u2009years, HR<jats:sub>total<\/jats:sub>\u2009=\u20091.60 [1.59; 1.62], mediation\u2009=\u200914.4%), drug use disorder in females (25\u201336\u2009years, HR<jats:sub>total<\/jats:sub>\u2009=\u20091.46 [1.44; 1.49], mediation\u2009=\u200911.2%), and major depression (25\u201336\u2009years) in females (HR<jats:sub>total<\/jats:sub>\u2009=\u20091.46 [1.44; 1.49], mediation\u2009=\u20097%) and males (HR<jats:sub>total<\/jats:sub>\u2009=\u20091.50 [1.47;1.52], mediation\u2009=\u20094.7%). While the direct effect of FGRS<jats:sub>SA<\/jats:sub> was higher at ages of 15\u201325, the mediation via psychiatric disorders was more prominent in later adulthood. Our study informs about the psychiatric illnesses via which genetic liability operates to impact suicide attempt risk, with distinct contributions according to age and sex.<\/jats:p>","DOI":"10.1002\/ajmg.b.32974","type":"journal-article","created":{"date-parts":[[2024,2,17]],"date-time":"2024-02-17T08:24:10Z","timestamp":1708158250000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mediational pathways between aggregate genetic liability and nonfatal suicide attempt: A Swedish population\u2010based cohort"],"prefix":"10.1002","volume":"195","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7773-4553","authenticated-orcid":false,"given":"S\u00e9verine","family":"Lannoy","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics Virginia Commonwealth University School of Medicine  Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Ohlsson","sequence":"additional","affiliation":[{"name":"Center for Primary Health Care Research Lund University  Malm\u00f6 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mallory","family":"Stephenson","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics Virginia Commonwealth University School of Medicine  Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Sundquist","sequence":"additional","affiliation":[{"name":"Center for Primary Health Care Research Lund University  Malm\u00f6 Sweden"},{"name":"Department of Family Medicine and Community Health Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"Department of Population Health Science and Policy Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Sundquist","sequence":"additional","affiliation":[{"name":"Center for Primary Health Care Research Lund University  Malm\u00f6 Sweden"},{"name":"Department of Family Medicine and Community Health Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"Department of Population Health Science and Policy Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4006-9710","authenticated-orcid":false,"given":"Alexis C.","family":"Edwards","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics Virginia Commonwealth University School of Medicine  Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,2,17]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psc.2008.02.001"},{"key":"e_1_2_10_3_1","unstructured":"Centers for Disease Control and Prevention. 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