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Aberrant DNA methylation of CpG sites has been associated with many psychiatric disorders including bipolar disorder (BD) and suicide. Using the SureSelect<jats:sup>XT<\/jats:sup> system, Methyl\u2010Seq, we investigated the DNA methylation status of CpG sites throughout the genome in 50 BD individuals (23 subjects who died by suicide and 27 subjects who died from other causes) and 31 nonpsychiatric controls. We identified differentially methylated regions (DMRs) from three analyses: (a) BD subjects compared to nonpsychiatric controls (BD\u2010NC), (b) BD subjects who died by suicide compared to nonpsychiatric controls (BDS\u2010NC), and (c) BDS subjects compared to BD subjects who died from other causes (BDS\u2010BDNS). One DMR from the BDS\u2010NC analysis, located in <jats:italic>ARHGEF38<\/jats:italic>, was significantly hypomethylated (23.4%) in BDS subjects. This finding remained significant after multiple testing (P<jats:sub>Bootstrapped<\/jats:sub> = 9.0 \u00d7 10<jats:sup>\u22123<\/jats:sup>), was validated using pyrosequencing, and was more significant in males. A secondary analysis utilized Ingenuity Pathway Analysis to identify enrichment in nominally significant DMRs. This identified an association with several pathways including axonal guidance signaling, calcium signaling, \u03b2\u2010adrenergic signaling, and opioid signaling. Our comprehensive study provides further support that DNA methylation alterations influence the risk for BD and suicide. However, further investigation is required to confirm these associations and identify their functional consequences.<\/jats:p>","DOI":"10.1002\/ajmg.b.32754","type":"journal-article","created":{"date-parts":[[2019,7,27]],"date-time":"2019-07-27T07:08:51Z","timestamp":1564211331000},"page":"496-507","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Differentially methylated regions in bipolar disorder and suicide"],"prefix":"10.1002","volume":"180","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9196-0028","authenticated-orcid":false,"given":"Marie E.","family":"Gaine","sequence":"first","affiliation":[{"name":"Department of Psychiatry University of Iowa Carver College of Medicine  Iowa City Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fayaz","family":"Seifuddin","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences Johns Hopkins School of Medicine  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarven","family":"Sabunciyan","sequence":"additional","affiliation":[{"name":"Center for Epigenetics Johns Hopkins School of Medicine  Baltimore Maryland"},{"name":"Department of Pediatrics Johns Hopkins School of Medicine  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard S.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences Johns Hopkins School of Medicine  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly S.","family":"Benke","sequence":"additional","affiliation":[{"name":"Department of Mental Health, Bloomberg School of Public Health Johns Hopkins University  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric T.","family":"Monson","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Iowa Carver College of Medicine  Iowa City Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter P.","family":"Zandi","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences Johns Hopkins School of Medicine  Baltimore Maryland"},{"name":"Department of Mental Health, Bloomberg School of Public Health Johns Hopkins University  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James B.","family":"Potash","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences Johns Hopkins School of Medicine  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia L.","family":"Willour","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Iowa Carver College of Medicine  Iowa City Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,7,27]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.32691"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2016.261"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13072-016-0107-z"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-244X-4-37"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra035354"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1089\/cap.2016.0079"},{"key":"e_1_2_7_8_1","unstructured":"Centers for Disease Control and Prevention N. 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