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Prenatal opioid exposure may have consequences for health and (neuro)development, including neonatal opioid withdrawal syndrome (NOWS). It is unknown which infants are at greatest risk for NOWS. DNA methylation (DNAm) is an epigenetic mark reflecting both allelic variation and environmental exposures, which may provide biomarkers for prenatal opioid exposure and infant NOWS. The placenta is an accessible, biologically relevant tissue in which to directly investigate the epigenetic effects of prenatal opioid exposure. Therefore, the aims of this study were to examine whether prenatal opioid exposure is associated with differential DNAm, including epigenetic age acceleration (EAA) in the placenta. We performed an epigenome-wide association study based on co-methylated regions and single CpG sites in placental samples from in utero opioid-exposed (n\u00a0=\u00a019) and nonexposed infants (n\u00a0=\u00a0143), correcting for potential confounders. We did not identify statistically significant differential DNAm profiles, but the strongest associations were found for cg06621211; cg18688392 (ZMIZ1, adjusted P\u00a0=\u00a0.068) and cg04460738 (KCNMA1, adjusted P\u00a0=\u00a0.068), although effect sizes were very small. One of these DNAm patterns (cg06621211) was in part under control of genetic variants through methylation quantitative trait loci. The involved single nucleotide polymorphism did not show significant associations in recent genome-wide association studies for phenotypes related to substance use, and the finding was not driven by potential co-occurring substance use based on sensitivity analyses. There was also no association between placental EAA and in utero opioid exposure. In conclusion, placental DNAm showed limited associations with in utero opioid exposure and NOWS diagnosis.<\/jats:p>","DOI":"10.1093\/eep\/dvaf021","type":"journal-article","created":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T11:52:04Z","timestamp":1756986724000},"source":"Crossref","is-referenced-by-count":2,"title":["Epigenome-wide association study of placental co-methylated regions in newborns for prenatal opioid exposure"],"prefix":"10.1093","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9307-0643","authenticated-orcid":false,"given":"Mandy","family":"Meijer","sequence":"first","affiliation":[{"name":"University of British Columbia Department of Medical Genetics, Faculty of Medicine, , Vancouver, BC V5Z 4H4 ,","place":["Canada"]},{"name":"British Columbia Children\u2019s Hospital Research Institute, University of British Columbia , Vancouver, BC V5Z 4H4 ,","place":["Canada"]},{"name":"Centre for Molecular Medicine and Therapeutics, University of British Columbia , Vancouver, BC V5Z 4H4 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaini","family":"Konwar","sequence":"additional","affiliation":[{"name":"University of British Columbia Department of Medical Genetics, Faculty of Medicine, , Vancouver, BC V5Z 4H4 ,","place":["Canada"]},{"name":"British Columbia Children\u2019s Hospital Research Institute, University of British Columbia , Vancouver, BC V5Z 4H4 ,","place":["Canada"]},{"name":"Centre for Molecular Medicine and Therapeutics, University of British Columbia , Vancouver, BC V5Z 4H4 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1285-1614","authenticated-orcid":false,"given":"Rebecca","family":"Asiimwe","sequence":"additional","affiliation":[{"name":"University of British Columbia Department of Medical Genetics, Faculty of Medicine, , Vancouver, BC V5Z 4H4 ,","place":["Canada"]},{"name":"British Columbia Children\u2019s Hospital Research Institute, University of British Columbia , Vancouver, BC V5Z 4H4 ,","place":["Canada"]},{"name":"Centre for Molecular Medicine and Therapeutics, University of British Columbia , Vancouver, BC V5Z 4H4 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Maclsaac","sequence":"additional","affiliation":[{"name":"University of British Columbia Department of Medical Genetics, Faculty of Medicine, , Vancouver, BC V5Z 4H4 ,","place":["Canada"]},{"name":"British Columbia Children\u2019s Hospital Research Institute, University of British Columbia , Vancouver, BC V5Z 4H4 ,","place":["Canada"]},{"name":"Centre for Molecular Medicine and Therapeutics, University of British Columbia , Vancouver, BC V5Z 4H4 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katia","family":"Ramadori","sequence":"additional","affiliation":[{"name":"University of British Columbia Department of Medical Genetics, Faculty of Medicine, , Vancouver, BC V5Z 4H4 ,","place":["Canada"]},{"name":"British Columbia Children\u2019s Hospital Research Institute, University of British Columbia , Vancouver, BC V5Z 4H4 ,","place":["Canada"]},{"name":"Centre for Molecular Medicine and Therapeutics, University of British Columbia , Vancouver, BC V5Z 4H4 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Lin","sequence":"additional","affiliation":[{"name":"University of British Columbia Department of Medical Genetics, Faculty of Medicine, , Vancouver, BC V5Z 4H4 ,","place":["Canada"]},{"name":"British Columbia Children\u2019s Hospital Research Institute, University of British Columbia , Vancouver, BC V5Z 4H4 ,","place":["Canada"]},{"name":"Centre for Molecular Medicine and Therapeutics, University of British Columbia , Vancouver, BC V5Z 4H4 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric L","family":"Garland","sequence":"additional","affiliation":[{"name":"University of California San Diego Department of Psychiatry, , San Diego, CA 92093 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendan","family":"Ostlund","sequence":"additional","affiliation":[{"name":"Pennsylvania State University Department of Psychology, , State College, PA 16802 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S","family":"Kobor","sequence":"additional","affiliation":[{"name":"University of British Columbia Department of Medical Genetics, Faculty of Medicine, , Vancouver, BC V5Z 4H4 ,","place":["Canada"]},{"name":"British Columbia Children\u2019s Hospital Research Institute, University of British Columbia , Vancouver, BC V5Z 4H4 ,","place":["Canada"]},{"name":"Centre for Molecular Medicine and Therapeutics, University of British Columbia , Vancouver, BC V5Z 4H4 ,","place":["Canada"]},{"name":"Edwin S. 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