{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T02:05:30Z","timestamp":1789005930447,"version":"build-2803163510"},"reference-count":25,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T00:00:00Z","timestamp":1697155200000},"content-version":"am","delay-in-days":365,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#am"},{"start":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T00:00:00Z","timestamp":1665619200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100005435","name":"Association of American Medical Colleges","doi-asserted-by":"publisher","award":["MM\u20101125\u201009\/09"],"award-info":[{"award-number":["MM\u20101125\u201009\/09"]}],"id":[{"id":"10.13039\/100005435","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000030","name":"Centers for Disease Control and Prevention","doi-asserted-by":"publisher","award":["U01DD001033"],"award-info":[{"award-number":["U01DD001033"]}],"id":[{"id":"10.13039\/100000030","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000030","name":"Centers for Disease Control and Prevention","doi-asserted-by":"publisher","award":["MM1125\u201009\/09"],"award-info":[{"award-number":["MM1125\u201009\/09"]}],"id":[{"id":"10.13039\/100000030","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01DD001033"],"award-info":[{"award-number":["U01DD001033"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["CA190214"],"award-info":[{"award-number":["CA190214"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005002","name":"California Department of Public Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>There is emerging evidence that children with complex congenital heart defects (CHDs) are at increased risk for childhood lymphoma, but the mechanisms underlying this association are unclear. Thus, we sought to evaluate the role of DNA methylation patterns on \u201cCHD\u2010lymphoma\u201d associations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>From &gt;3 million live births (1988\u20132004) in California registry linkages, we obtained newborn dried bloodspots from eight children with CHD\u2010lymphoma through the California BioBank. We performed case\u2013control epigenome\u2010wide association analyses (EWAS) using two comparison groups with reciprocal discovery and validation to identify differential methylation associated with CHD\u2010lymphoma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>After correction for multiple testing at the discovery and validation stages, individuals with CHD\u2010lymphoma had differential newborn methylation at six sites relative to two comparison groups. Our top finding was significant in both EWAS and indicates <jats:italic>PPFIA1<\/jats:italic> cg25574765 was hypomethylated among individuals with CHD\u2010lymphoma (mean beta\u00a0=\u00a00.04) relative to both unaffected individuals (mean beta\u00a0=\u00a00.93, <jats:italic>p<\/jats:italic>\u00a0=\u00a01.5\u2009\u00d7\u200910<jats:sup>\u221212<\/jats:sup>) and individuals with complex CHD (mean beta\u00a0=\u00a00.95, <jats:italic>p<\/jats:italic>\u00a0=\u00a03.8\u2009\u00d7\u200910<jats:sup>\u22128<\/jats:sup>). <jats:italic>PPFIA1<\/jats:italic> encodes a ubiquitously expressed liprin protein in one of the most commonly amplified regions in many cancers (11q13). Further, cg25574765 is a proposed marker of pre\u2010eclampsia, a maternal CHD risk factor that has not been fully evaluated for lymphoma risk in offspring, and the tumor microenvironment that may drive immune cell malignancies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We identified associations between molecular changes present in the genome at birth and risk of childhood lymphoma among those with CHD. Our findings also highlight novel perinatal exposures that may underlie methylation changes in CHD predisposing to lymphoma.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdr2.2105","type":"journal-article","created":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T09:24:49Z","timestamp":1665653089000},"page":"1434-1439","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Differential newborn <scp>DNA<\/scp> methylation among individuals with complex congenital heart defects and childhood lymphoma"],"prefix":"10.1002","volume":"114","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0129-9860","authenticated-orcid":false,"given":"Melissa A.","family":"Richard","sequence":"first","affiliation":[{"name":"Department of Pediatrics Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Stanford University School of Medicine  Palo Alto California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pagna","family":"Sok","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics Indiana University  Bloomington Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzan L.","family":"Carmichael","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Stanford University School of Medicine  Palo Alto California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"von Behren","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peggy","family":"Reynolds","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul G.","family":"Fisher","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Stanford University School of Medicine  Palo Alto California USA"},{"name":"Department of Neurology Stanford University School of Medicine  Palo Alto California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3387-6629","authenticated-orcid":false,"given":"R. Thomas","family":"Collins","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Stanford University School of Medicine  Palo Alto California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte A.","family":"Hobbs","sequence":"additional","affiliation":[{"name":"Rady Children's Institute for Genomic Medicine  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Luke","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology, and Reproductive Biology, College of Human Medicine Michigan State University  East Lansing Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7438-4914","authenticated-orcid":false,"given":"Gary M.","family":"Shaw","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Stanford University School of Medicine  Palo Alto California 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