{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T23:59:47Z","timestamp":1783036787798,"version":"3.54.6"},"reference-count":45,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,3,2]],"date-time":"2016-03-02T00:00:00Z","timestamp":1456876800000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Marriott Family Foundation"},{"name":"Mayo Clinic's Center for Individualized Medicine"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bipolar Disorders"],"published-print":{"date-parts":[[2016,3]]},"abstract":"Objectives<\/jats:title>Bipolar disorder (BD<\/jats:styled-content>) is a complex disease associated with various hereditary traits, including a higher body mass index (BMI<\/jats:styled-content>). In a prior genome\u2010wide association study, we found that BMI<\/jats:styled-content> modified the association of rs12772424 \u2013 a common variant in the gene encoding transcription factor 7\u2010like 2 (TCF<\/jats:styled-content>7L2<\/jats:italic>) \u2013 with risk for BD<\/jats:styled-content>. TCF<\/jats:styled-content>7L2<\/jats:italic> is a transcription factor in the canonical Wnt pathway, involved in multiple disorders, including diabetes, cancer and psychiatric conditions. Here, using an independent sample, we evaluated 26 TCF<\/jats:styled-content>7L2<\/jats:italic> single nucleotide polymorphisms (SNP<\/jats:styled-content>s) to explore further the association of BD<\/jats:styled-content> with the TCF<\/jats:styled-content>7L2<\/jats:italic>\u2013BMI<\/jats:styled-content> interaction.<\/jats:p><\/jats:sec>Methods<\/jats:title>Using a sample of 662 BD<\/jats:styled-content> cases and 616 controls, we conducted SNP<\/jats:styled-content>\u2010level and gene\u2010level tests to assess the evidence for an association between BD<\/jats:styled-content> and the interaction of BMI<\/jats:styled-content> and genetic variation in TCF<\/jats:styled-content>7L2<\/jats:italic>. We also explored the potential mechanism behind the detected associations using human brain expression quantitative trait loci (eQTL<\/jats:styled-content>) analysis.<\/jats:p><\/jats:sec>Results<\/jats:title>The analysis provided independent evidence of an rs12772424\u2013BMI<\/jats:styled-content> interaction (p = 0.011). Furthermore, while overall there was no evidence for SNP<\/jats:styled-content> marginal effects on BD<\/jats:styled-content>, the TCF<\/jats:styled-content>7L2<\/jats:italic>\u2013BMI<\/jats:styled-content> interaction was significant at the gene level (p = 0.042), with seven of the 26 SNP<\/jats:styled-content>s showing SNP<\/jats:styled-content>\u2013BMI<\/jats:styled-content> interaction effects with p < 0.05. The strongest evidence of interaction was observed for rs7895307 (p = 0.006). TCF<\/jats:styled-content>7L2<\/jats:italic> expression showed a significant enrichment of association with the expression of other genes in the Wnt canonical pathway.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>The current study provides further evidence suggesting that TCF<\/jats:styled-content>7L2<\/jats:italic> involvement in BD<\/jats:styled-content> risk may be regulated by BMI<\/jats:styled-content>. Detailed, prospective assessment of BMI<\/jats:styled-content>, comorbidity, and other possible contributing factors is necessary to explain fully the mechanisms underlying this association.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bdi.12368","type":"journal-article","created":{"date-parts":[[2016,3,2]],"date-time":"2016-03-02T14:35:51Z","timestamp":1456929351000},"page":"124-135","source":"Crossref","is-referenced-by-count":27,"title":["Accumulating evidence for a role of TCF<\/scp>7L2 variants in bipolar disorder with elevated body mass index"],"prefix":"10.1111","volume":"18","author":[{"given":"Alfredo B","family":"Cuellar\u2010Barboza","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Psychology Mayo Clinic Rochester MN USA"},{"name":"Department of Psychiatry University Hospital Universidad Autonoma de Nuevo Leon Monterrey Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacey J","family":"Winham","sequence":"additional","affiliation":[{"name":"Department of Health Sciences Research Mayo Clinic Rochester MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan L","family":"McElroy","sequence":"additional","affiliation":[{"name":"Lindner Center of HOPE Mason OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer R","family":"Geske","sequence":"additional","affiliation":[{"name":"Department of Health Sciences Research Mayo Clinic Rochester MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory D","family":"Jenkins","sequence":"additional","affiliation":[{"name":"Department of Health Sciences Research Mayo Clinic Rochester MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin L","family":"Colby","sequence":"additional","affiliation":[{"name":"Department of Health Sciences Research Mayo Clinic Rochester MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0167-4501","authenticated-orcid":false,"given":"Miguel L","family":"Prieto","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychology Mayo Clinic Rochester MN USA"},{"name":"Departamento de Psiquiatr\u00eda Facultad de Medicina Universidad de los Andes"},{"name":"Cl\u00ednica Universidad de los Andes Unidad de Salud Mental Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Euijung","family":"Ryu","sequence":"additional","affiliation":[{"name":"Department of Health Sciences Research Mayo Clinic Rochester MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie M","family":"Cunningham","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic Rochester Rochester MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark 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