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The objective of this study was to perform a genome-wide association study of this comorbidity (<jats:italic>Com<\/jats:italic>), substance use alone (<jats:italic>Subs<\/jats:italic>), and psychiatric symptomatology alone (<jats:italic>Psych<\/jats:italic>) in the Mexican population. The study included 3914 individuals of Mexican descent. Genotyping was carried out using the PsychArray microarray and genome-wide correlations were calculated. Genome-wide associations were analyzed using multiple logistic models, polygenic risk scores (PRSs) were evaluated using multinomial models, and vertical pleiotropy was evaluated by generalized summary-data-based Mendelian randomization. Brain DNA methylation quantitative loci (brain meQTL) were also evaluated in the prefrontal cortex. Genome-wide correlation and vertical pleiotropy were found between all traits. No genome-wide association signals were found, but 64 single-nucleotide polymorphism (SNPs) reached nominal associations (<jats:italic>p<\/jats:italic>\u2009&lt;\u20095.00e\u221205). The SNPs associated with each trait were independent, and the individuals with high PRSs had a higher prevalence of tobacco and alcohol use. In the multinomial models all of the PRSs (<jats:italic>Subs<\/jats:italic>-PRS, <jats:italic>Com<\/jats:italic>-PRS, and <jats:italic>Psych<\/jats:italic>-PRS) were associated with all of the traits. Brain meQTL of the <jats:italic>Subs<\/jats:italic>-associated SNPs had an effect on the genes enriched in insulin signaling pathway, and that of the <jats:italic>Psych<\/jats:italic>-associated SNPs had an effect on the Fc gamma receptor phagocytosis pathway.<\/jats:p>","DOI":"10.1038\/s41598-021-85881-4","type":"journal-article","created":{"date-parts":[[2021,3,24]],"date-time":"2021-03-24T11:04:07Z","timestamp":1616583847000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Genome-wide association study of psychiatric and substance use comorbidity in Mexican individuals"],"prefix":"10.1038","volume":"11","author":[{"given":"Jos\u00e9 Jaime","family":"Mart\u00ednez-Maga\u00f1a","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alma Delia","family":"Genis-Mendoza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge Ameth","family":"Villatoro Vel\u00e1zquez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marycarmen","family":"Bustos-Gami\u00f1o","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isela Esther","family":"Ju\u00e1rez-Rojop","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos Alfonso","family":"Tovilla-Zarate","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emmanuel","family":"Sarmiento","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erasmo","family":"Saucedo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oscar","family":"Rodr\u00edguez-Mayoral","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clara","family":"Fleiz-Bautista","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatriz","family":"Camarena","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alejandro","family":"Aguilar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thelma Beatriz","family":"Gonzalez-Castro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Elena","family":"Medina-Mora","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Humberto","family":"Nicolini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,3,24]]},"reference":[{"key":"85881_CR1","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1080\/09595230600944461","volume":"25","author":"E Jan\u00e9-Llopis","year":"2006","unstructured":"Jan\u00e9-Llopis, E. & Matytsina, I. 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