{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T23:04:33Z","timestamp":1767913473138,"version":"3.49.0"},"reference-count":38,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,4,12]],"date-time":"2014-04-12T00:00:00Z","timestamp":1397260800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Stanley Center for Psychiatric Research","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bipolar Disorders"],"published-print":{"date-parts":[[2014,9]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>Family and genetic studies indicate overlapping liability for major depressive disorder and bipolar disorder. The purpose of the present study was to determine whether this shared genetic liability influences clinical presentation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A polygenic risk score for bipolar disorder, derived from a large genome\u2010wide association meta\u2010analysis, was generated for each subject of European\u2013American ancestry (n\u00a0=\u00a01,274) in the Sequential Treatment Alternatives to Relieve Depression study (STAR*D) outpatient major depressive disorder cohort. A hypothesis\u2010driven approach was used to test for association between bipolar disorder risk score and features of depression associated with bipolar disorder in the literature. Follow\u2010up analyses were performed in two additional cohorts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A generalized linear mixed model including seven features hypothesized to be associated with bipolar spectrum illness was significantly associated with bipolar polygenic risk score [<jats:italic>F\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>2.07, degrees of freedom (df)\u00a0=\u00a07, p\u00a0=\u00a00.04]. Features included early onset, suicide attempt, recurrent depression, atypical depression, subclinical mania, subclinical psychosis, and severity. <jats:italic>Post\u2010hoc<\/jats:italic> univariate analyses demonstrated that the major contributors to this omnibus association were onset of illness at age \u2264 18\u00a0years [odds ratio (OR)\u00a0=\u00a01.2, p\u00a0=\u00a00.003], history of suicide attempt (OR\u00a0=\u00a01.21, p\u00a0=\u00a00.03), and presence of at least one manic symptom (OR\u00a0=\u00a01.16, p\u00a0=\u00a00.02). The maximal variance in these traits explained by polygenic score ranged from 0.8% to 1.1%. However, analyses in two replication cohorts testing a five\u2010feature model did not support this association.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Bipolar genetic loading appeared to be associated with bipolar\u2010like presentation in major depressive disorder in the primary analysis. However, the results were at most inconclusive because of lack of replication. Replication efforts were challenged by different ascertainment and assessment strategies in the different cohorts. The methodological approach described here may prove useful in applying genetic data to clarify psychiatric nosology in future studies.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bdi.12201","type":"journal-article","created":{"date-parts":[[2014,4,12]],"date-time":"2014-04-12T08:01:39Z","timestamp":1397289699000},"page":"608-616","source":"Crossref","is-referenced-by-count":25,"title":["Bipolar polygenic loading and bipolar spectrum features in major depressive disorder"],"prefix":"10.1111","volume":"16","author":[{"given":"Anna","family":"Wiste","sequence":"first","affiliation":[{"name":"Psychiatric and Neurodevelopmental Genetics Unit Center for Human Genetic Research Boston MA USA"},{"name":"Center for Experimental Drugs and Diagnostics Department of Psychiatry Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elise B","family":"Robinson","sequence":"additional","affiliation":[{"name":"Analytical and Translational Genetics Unit Massachusetts General Hospital Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuri","family":"Milaneschi","sequence":"additional","affiliation":[{"name":"Department of Psychiatry VU University Medical Center Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Meier","sequence":"additional","affiliation":[{"name":"Department of Genetic Epidemiology in Psychiatry Central Institute of Mental Health Medical Faculty Mannheim\/Heidelberg University Mannheim Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephan","family":"Ripke","sequence":"additional","affiliation":[{"name":"Analytical and Translational Genetics Unit Massachusetts General Hospital Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caitlin C","family":"Clements","sequence":"additional","affiliation":[{"name":"Psychiatric and Neurodevelopmental Genetics Unit Center for Human Genetic Research Boston MA USA"},{"name":"Center for Experimental Drugs and Diagnostics Department of Psychiatry Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Garrett M","family":"Fitzmaurice","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Harvard School of Public Health Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcella","family":"Rietschel","sequence":"additional","affiliation":[{"name":"Department of Genetic Epidemiology in Psychiatry Central Institute of Mental Health Medical Faculty Mannheim\/Heidelberg University Mannheim Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brenda W","family":"Penninx","sequence":"additional","affiliation":[{"name":"Department of Psychiatry VU University Medical Center Amsterdam The Netherlands"},{"name":"Department of Psychiatry Leiden University Medical Center Leiden"},{"name":"Department of Psychiatry University Medical Center of Groningen Groningen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jordan W","family":"Smoller","sequence":"additional","affiliation":[{"name":"Psychiatric and Neurodevelopmental Genetics Unit Center for Human Genetic Research Boston MA USA"},{"name":"Department of Psychiatry Massachusetts General Hospital Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roy H","family":"Perlis","sequence":"additional","affiliation":[{"name":"Psychiatric and Neurodevelopmental Genetics Unit Center for Human Genetic Research Boston MA USA"},{"name":"Center for Experimental Drugs and Diagnostics Department of Psychiatry Boston MA 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