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However, the mechanisms underlying these comorbidities with BD are not well known. Certain genetic variants may have pleiotropic effects, increasing the risk of BD and other medical illnesses simultaneously. In this study, we evaluated the association of BD-susceptibility genetic variants with various medical conditions that tend to co-exist with BD, using electronic health records (EHR) data linked to genome-wide single-nucleotide polymorphism (SNP) data. Data from 7316 Caucasian subjects were used to test the association of 19 EHR-derived phenotypes with 34 SNPs that were previously reported to be associated with BD. After Bonferroni multiple testing correction, <jats:italic>P<\/jats:italic>&lt;7.7 \u00d7 10<jats:sup>\u22125<\/jats:sup> was considered statistically significant. The top association findings suggested that the BD risk alleles at SNP rs4765913 in <jats:italic>CACNA1C<\/jats:italic> gene and rs7042161 in <jats:italic>SVEP1<\/jats:italic> may be associated with increased risk of \u2018cardiac dysrhythmias\u2019 (odds ratio (OR)=1.1, <jats:italic>P<\/jats:italic>=3.4 \u00d7 10<jats:sup>\u22123<\/jats:sup>) and \u2018essential hypertension\u2019 (OR=1.1, <jats:italic>P<\/jats:italic>=3.5 \u00d7 10<jats:sup>\u22123<\/jats:sup>), respectively. Although these associations are not statistically significant after multiple testing correction, both genes have been previously implicated with cardiovascular phenotypes. Moreover, we present additional evidence supporting these associations, particularly the association of the <jats:italic>SVEP1<\/jats:italic> SNP with hypertension. This study shows the potential for EHR-based analyses of large cohorts to discover pleiotropic effects contributing to complex psychiatric traits and commonly co-occurring medical conditions.<\/jats:p>","DOI":"10.1038\/tp.2016.138","type":"journal-article","created":{"date-parts":[[2016,8,16]],"date-time":"2016-08-16T13:45:05Z","timestamp":1471355105000},"page":"e870-e870","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Leveraging electronic health records to study pleiotropic effects on bipolar disorder and medical comorbidities"],"prefix":"10.1038","volume":"6","author":[{"given":"M L","family":"Prieto","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E","family":"Ryu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G D","family":"Jenkins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Batzler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M M","family":"Nassan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A B","family":"Cuellar-Barboza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Pathak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S L","family":"McElroy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M A","family":"Frye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J M","family":"Biernacka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,8,16]]},"reference":[{"key":"BFtp2016138_CR1","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1001\/jamapsychiatry.2013.1394","volume":"70","author":"C Crump","year":"2013","unstructured":"Crump C, Sundquist K, Winkleby MA, Sundquist J . 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