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Some hypothesis-driven investigations of epigenetic markers for treatment response have been previously made, but genome-wide approaches remain unexplored. Healthy participants (<jats:italic>n<\/jats:italic>\u2009=\u2009112) and MDD patients (<jats:italic>n<\/jats:italic>\u2009=\u2009211) between 18\u201360 years old were recruited for an 8-week trial of escitalopram treatment. Responders and non-responders were identified using differential Montgomery-\u00c5sberg Depression Rating Scale scores before and after treatment. Genome-wide DNA methylation and gene expression analyses were assessed using the Infinium MethylationEPIC Beadchip and HumanHT-12 v4 Expression Beadchip, respectively, on pre-treatment peripheral blood DNA and RNA samples. Differentially methylated positions (DMPs) located in regions of differentially expressed genes between responders (<jats:italic>n<\/jats:italic>\u2009=\u200982) and non-responders (<jats:italic>n<\/jats:italic>\u2009=\u200995) were identified, and technically validated using a targeted sequencing approach. Three DMPs located in the genes<jats:italic>CHN2<\/jats:italic>(cg23687322,<jats:italic>p<\/jats:italic>\u2009=\u20090.00043 and cg06926818,<jats:italic>p<\/jats:italic>\u2009=\u20090.0014) and<jats:italic>JAK2<\/jats:italic>(cg08339825,<jats:italic>p<\/jats:italic>\u2009=\u20090.00021) were the most significantly associated with mRNA expression changes and subsequently validated. Replication was then conducted with non-responders (<jats:italic>n<\/jats:italic>\u2009=\u200976) and responders (<jats:italic>n<\/jats:italic>\u2009=\u200971) in an external cohort that underwent a similar antidepressant trial. One<jats:italic>CHN2<\/jats:italic>site (cg06926818;<jats:italic>p<\/jats:italic>\u2009=\u20090.03) was successfully replicated. Our findings indicate that differential methylation at CpG sites upstream of the<jats:italic>CHN2<\/jats:italic>and<jats:italic>JAK2<\/jats:italic>TSS regions are possible peripheral predictors of antidepressant treatment response. Future studies can provide further insight on robustness of our candidate biomarkers, and greater characterization of functional components.<\/jats:p>","DOI":"10.1038\/s41398-019-0589-0","type":"journal-article","created":{"date-parts":[[2019,10,8]],"date-time":"2019-10-08T09:02:50Z","timestamp":1570525370000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Integrated genome-wide methylation and expression analyses reveal functional predictors of response to antidepressants"],"prefix":"10.1038","volume":"9","author":[{"given":"Chelsey","family":"Ju","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura M.","family":"Fiori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raoul","family":"Belzeaux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Francois","family":"Theroux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary Gang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahia","family":"Aouabed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Blier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faranak","family":"Farzan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benicio N.","family":"Frey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Giacobbe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7142-4669","authenticated-orcid":false,"given":"Raymond W.","family":"Lam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Leri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenda M.","family":"MacQueen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6884-171X","authenticated-orcid":false,"given":"Roumen","family":"Milev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sagar V.","family":"Parikh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Rotzinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio N.","family":"Soares","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolf","family":"Uher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4182-4535","authenticated-orcid":false,"given":"Qingqin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane A.","family":"Foster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sidney H.","family":"Kennedy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4075-2736","authenticated-orcid":false,"given":"Gustavo","family":"Turecki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,10,8]]},"reference":[{"key":"589_CR1","unstructured":"World Health Organization W. 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