{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:33:44Z","timestamp":1791923624440,"version":"4.3.4"},"reference-count":39,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2014,7,11]],"date-time":"2014-07-11T00:00:00Z","timestamp":1405036800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bipolar Disorders"],"published-print":{"date-parts":[[2015,3]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>Accumulating evidence implicates the potassium voltage\u2010gated channel, KQT\u2010like subfamily, member 2 and 3 (<jats:italic>KCNQ2<\/jats:italic> and <jats:italic>KCNQ3<\/jats:italic>) genes in the etiology of bipolar disorder (<jats:styled-content style=\"fixed-case\">BPD<\/jats:styled-content>). Reduced <jats:italic><jats:styled-content style=\"fixed-case\">KCNQ<\/jats:styled-content>2<\/jats:italic> or <jats:italic><jats:styled-content style=\"fixed-case\">KCNQ<\/jats:styled-content>3<\/jats:italic> gene expression might lead to a loss of inhibitory M\u2010current and an increase in neuronal hyperexcitability in disease. The goal of the present study was to evaluate epigenetic and gene expression associations of the <jats:italic><jats:styled-content style=\"fixed-case\">KCNQ<\/jats:styled-content>2<\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">KCNQ<\/jats:styled-content>3<\/jats:italic> genes with <jats:styled-content style=\"fixed-case\">BPD<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>DNA methylation and gene expression levels of alternative transcripts of <jats:italic>KCNQ2<\/jats:italic> and <jats:italic>KCNQ3<\/jats:italic> capable of binding the ankyrin G (<jats:italic>ANK3<\/jats:italic>) gene were evaluated using bisulfite pyrosequencing and the quantitative real\u2010time polymerase chain reaction in the postmortem prefrontal cortex of subjects with BPD and matched controls from the McLean Hospital. Replication analyses of DNA methylation findings were performed using prefrontal cortical DNA obtained from the Stanley Medical Research Institute.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Significantly lower expression was observed in <jats:italic>KCNQ3<\/jats:italic>, but not <jats:italic>KCNQ2<\/jats:italic>. DNA methylation analysis of CpGs within an alternative exonic region of <jats:italic>KCNQ3<\/jats:italic> exon 11 demonstrated significantly lower methylation in BPD, and correlated significantly with <jats:italic>KCNQ3 <\/jats:italic><jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> levels. Lower <jats:italic>KCNQ3<\/jats:italic> exon 11 DNA methylation was observed in the Stanley Medical Research Institute replication cohort, although only after correcting for mood stabilizer status. Mood stabilizer treatment in rats resulted in a slight DNA methylation increase at the syntenic <jats:italic>KCNQ3<\/jats:italic> exon 11 region, which subsequent analyses suggested could be the result of alterations in neuronal proportion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The results of the present study suggest that epigenetic alterations in the <jats:italic><jats:styled-content style=\"fixed-case\">KCNQ<\/jats:styled-content>3<\/jats:italic> gene may be important in the etiopathogenesis of <jats:styled-content style=\"fixed-case\">BPD<\/jats:styled-content> and highlight the importance of controlling for medication and cellular composition\u2010induced heterogeneity in psychiatric studies of the brain.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bdi.12230","type":"journal-article","created":{"date-parts":[[2014,7,11]],"date-time":"2014-07-11T08:51:31Z","timestamp":1405068691000},"page":"150-159","source":"Crossref","is-referenced-by-count":46,"title":["<scp>DNA<\/scp> methylation and expression of <i><scp>KCNQ<\/scp>3<\/i> in bipolar disorder"],"prefix":"10.1111","volume":"17","author":[{"given":"Zachary","family":"Kaminsky","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences Johns Hopkins University Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilenna","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences Johns Hopkins University Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranjana","family":"Verma","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Physiology and Genetics Uniformed Services 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