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Past research suggests methylmercury exposure and DNA methylation (DNAm) levels are each associated with ADHD in children, yet whether they interact to affect ADHD is unknown. Leveraging data from a longitudinal cohort of children in Mexico, this novel epigenetic\u2013environment interaction study identified significant interactions between childhood mercury exposure (measured at 6\u201312\u2009years of age) and adolescent blood leukocyte DNAm in their association with sustained attention [quantified via the Conners continuous performance test, 3rd edition (CPT3)] measured on average 5.6\u2009\u00b1\u20090.99\u2009years later. Using adjusted linear regression, we assessed associations between hair and urine mercury concentrations and CPT3 scores reflecting inattention, impulsivity, vigilance, and sustained attention (N\u2009=\u2009399). We then tested the interaction between mercury and DNAm at loci previously associated with the CPT3 outcomes (N\u2009=\u2009374). Significant associations between mercury and CPT3 differed in magnitude and direction depending on the mercury biomarker and CPT3 variable. These associations often differed by gender. For example, urine mercury was positively associated with vigilance scores in males [\u03b2\u2009=\u20091.31(SE\u2009=\u20090.65), P\u2009=\u2009.045] but not in females [\u03b2\u2009=\u2009\u22120.20 (SE\u2009=\u20090.81), P\u2009=\u2009.80). In all children, three significant mercury\u2013DNAm interactions were identified for either inattention or vigilance outcomes. Among females, 155 significant interaction terms were identified for the inattention models. In males, three significant interactions were identified for the impulsivity model. Overall, results suggest in some cases DNAm can influence the association between mercury exposure and ADHD-like symptoms.<\/jats:p>","DOI":"10.1093\/eep\/dvaf011","type":"journal-article","created":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T07:53:51Z","timestamp":1745394831000},"source":"Crossref","is-referenced-by-count":5,"title":["Interaction of mercury exposure and DNA methylation with sustained attention in children in a novel analysis of epigenetic susceptibility"],"prefix":"10.1093","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8546-7675","authenticated-orcid":false,"given":"Jessa V","family":"Ehlinger","sequence":"first","affiliation":[{"name":"Environmental Health Sciences, University of Michigan , Ann Arbor, MI 48109,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8289-9253","authenticated-orcid":false,"given":"Jaclyn M","family":"Goodrich","sequence":"additional","affiliation":[{"name":"Environmental Health Sciences, University of Michigan , Ann Arbor, MI 48109,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana C","family":"Dolinoy","sequence":"additional","affiliation":[{"name":"Environmental Health Sciences, University of Michigan , Ann Arbor, MI 48109,","place":["United States"]},{"name":"Nutritional Sciences, University of Michigan , Ann Arbor, MI 48109,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah J","family":"Watkins","sequence":"additional","affiliation":[{"name":"Environmental Health Sciences, University of Michigan , Ann Arbor, MI 48109,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandra","family":"Cantoral","sequence":"additional","affiliation":[{"name":"Department of Health, Iberoamerican University , M\u00e9xico City 01219,","place":["M\u00e9xico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Mercado-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Center for Nutrition and Health Research, National Institute of Public Health , Cuernavaca, Morelos 62100,","place":["M\u00e9xico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niladri","family":"Basu","sequence":"additional","affiliation":[{"name":"Agriculture and Environmental Sciences, McGill University , Montreal, QC H9X 3V9,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha M","family":"T\u00e9llez-Rojo","sequence":"additional","affiliation":[{"name":"Center for Nutrition and Health Research, National Institute of Public Health , Cuernavaca, Morelos 62100,","place":["M\u00e9xico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen E","family":"Peterson","sequence":"additional","affiliation":[{"name":"Environmental Health Sciences, University of Michigan , Ann Arbor, MI 48109,","place":["United States"]},{"name":"Nutritional Sciences, University of Michigan , Ann Arbor, MI 48109,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,4,24]]},"reference":[{"key":"2025103008510658900_R1","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1177\/10870547221085503","article-title":"ADHD in adults: a systematic review and meta-analysis of prevalence studies in outpatient psychiatric clinics","volume":"26","author":"Adamis","year":"2022","journal-title":"J Attention Disord"},{"key":"2025103008510658900_R2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.15585\/mmwr.su7102a1","article-title":"Mental health surveillance among children\u2014United States, 2013\u20132019","volume":"71","author":"Bitsko","year":"2022","journal-title":"MMWR 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