{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T08:05:47Z","timestamp":1753862747782,"version":"3.41.2"},"reference-count":71,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,4,29]],"date-time":"2019-04-29T00:00:00Z","timestamp":1556496000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Genomic Medicine","award":["20\/2014\/I"],"award-info":[{"award-number":["20\/2014\/I"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2019,6]]},"abstract":"Abstract<\/jats:title>Introduction<\/jats:title>Several studies indicate that polygenic obesity is linked to fat\u2010mass and obesity\u2010associated (FTO<\/jats:styled-content><\/jats:italic>) genetic variants. Nevertheless, the link between variants in FTO<\/jats:styled-content><\/jats:italic> and mental disorders has been barely explored. The present work aims to determine whether FTO<\/jats:styled-content><\/jats:italic> genetic variants are associated with bipolar disorder and obesity, and to perform an in silico prediction of variant\u2010dependent functional impact on the developing brain transcriptome.<\/jats:p><\/jats:sec>Methods<\/jats:title>Four hundred and forty\u2010six Mexican mestizos were included in a genetic association analysis. SNP<\/jats:styled-content>\u2010sequence kernel association test and linear mixed models were implemented for genetic association assessment. For functional impact prediction, we analyzed the mapping of regulatory elements, the modification of binding sites of transcription factors and the expression of transcription factors in the brain developing transcriptome, searching on different databases.<\/jats:p><\/jats:sec>Results<\/jats:title>In the set\u2010based analysis, we found different associated regions to BD<\/jats:styled-content> (bipolar disorder) and obesity. The promoter flanking region of FTO<\/jats:styled-content><\/jats:italic> intron 1 was associated with differential effects on BMI<\/jats:styled-content>, while intron 2 of RPGRIP<\/jats:styled-content>1L<\/jats:italic> and FTO<\/jats:styled-content><\/jats:italic> upstream regions were associated with BD<\/jats:styled-content>. The prediction analysis showed that FTO<\/jats:styled-content><\/jats:italic> BD<\/jats:styled-content>\u2010associated variants disturb binding sites of SP<\/jats:styled-content>1<\/jats:italic> and SP<\/jats:styled-content>2;<\/jats:italic> obesity\u2010associated variants, on the other hand, disturb binding sites of FOXP<\/jats:styled-content>1,<\/jats:italic> which are transcription factors highly expressed during prenatal development stages of the brain.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Our results suggest a possible effect of FTO<\/jats:styled-content><\/jats:italic> variants on neurodevelopment in obesity and bipolar disorder, which gives new insights into the molecular mechanism underlying this association.<\/jats:p><\/jats:sec>","DOI":"10.1002\/brb3.1249","type":"journal-article","created":{"date-parts":[[2019,4,29]],"date-time":"2019-04-29T20:39:30Z","timestamp":1556570370000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Differential effects on neurodevelopment of FTO<\/scp><\/i> variants in obesity and bipolar disorder suggested by in silico prediction of functional impact: An analysis in Mexican population"],"prefix":"10.1002","volume":"9","author":[{"given":"Erasmo","family":"Saucedo\u2010Uribe","sequence":"first","affiliation":[{"name":"Center of Advanced Neurosciences Department of Psychiatry Autonomous University of Nuevo Leon Hospital Universitario \u201cDr. Jos\u00e9 Eleuterio Gonz\u00e1lez\u201d Monterrey Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alma Delia","family":"Genis\u2010Mendoza","sequence":"additional","affiliation":[{"name":"Laboratory of Genomics of Psychiatric and Neurodegenerative Diseases National Institute of Genomic Medicine Mexico City Mexico"},{"name":"Children's Psychiatric Hospital \u201cDr. Juan N. 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