{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T12:40:58Z","timestamp":1760013658005,"version":"3.41.2"},"reference-count":28,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,7,28]],"date-time":"2024-07-28T00:00:00Z","timestamp":1722124800000},"content-version":"vor","delay-in-days":27,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Prior studies report associations of maternal serum Lamin A, encoded by the <jats:italic>LMNA<\/jats:italic> gene, with fetal congenital heart disease (CHD). It is unknown whether DNA methylation (DNAm) of cytosine\u2010phosphate\u2010guanine (CpG) sites in <jats:italic>LMNA<\/jats:italic> impacts the CHD susceptibility.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We investigated the associations of <jats:italic>LMNA<\/jats:italic> DNAm with CHD using publicly available data of CHD cases (<jats:italic>n<\/jats:italic>\u2009=\u2009197) and controls (<jats:italic>n<\/jats:italic>\u2009=\u2009134) from the Gene Expression Omnibus repository. Peripheral blood DNAm was measured using Illumina 850\u2009K BeadChip for cases and 450\u2009K BeadChip for controls. We tested 31 <jats:italic>LMNA<\/jats:italic> CpGs to identify differences in DNAm between cases and controls using linear regression correcting for multiple testing with false discovery rate (FDR). In a case\u2010only analysis, we tested the variations in <jats:italic>LMNA<\/jats:italic> DNAm between CHD subtypes. To identify the consistency of DNAm across tissue types we compared peripheral blood (<jats:italic>n<\/jats:italic>\u2009=\u2009197) and heart tissue DNAm (<jats:italic>n<\/jats:italic>\u2009=\u200920) in CHD cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>After adjusting for age, sex, and cell types there were significant differences in 17 of the 31 <jats:italic>LMNA<\/jats:italic> CpGs between CHD cases and controls (FDR <jats:italic>p<\/jats:italic>\u2009\u2264\u2009.05). We identified lower DNAm of cg09820673 at 3\u2032 UTR for hypoplastic left heart syndrome compared to other CHD subtypes. Three CpGs exhibited uniform DNAm in blood and heart tissues in cases. Eleven CpGs showed changes in the same direction in blood and heart tissues in cases compared to controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We identify statistically significant differences in <jats:italic>LMNA<\/jats:italic> DNAm between CHD cases and controls. Future studies should investigate the role of maternal <jats:italic>LMNA<\/jats:italic> DNAm in CHD development.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdr2.2381","type":"journal-article","created":{"date-parts":[[2024,7,29]],"date-time":"2024-07-29T04:59:04Z","timestamp":1722229144000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>DNA<\/scp> methylation of the Lamin A\/C gene is associated with congenital heart disease"],"prefix":"10.1002","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6649-4555","authenticated-orcid":false,"given":"Nandini","family":"Mukherjee","sequence":"first","affiliation":[{"name":"Department of Epidemiology, Fay W. Boozman College of Public Health University of Arkansas for Medical Sciences  Little Rock Arkansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6805-2611","authenticated-orcid":false,"given":"Elijah H.","family":"Bolin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Section of Cardiology University of Arkansas for Medical Sciences and Arkansas Children's Research Institute  Little Rock Arkansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amna","family":"Qasim","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Section of Cardiology University of Arkansas for Medical Sciences and Arkansas Children's Research Institute  Little Rock Arkansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammed S.","family":"Orloff","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Fay W. Boozman College of Public Health University of Arkansas for Medical Sciences  Little Rock Arkansas USA"},{"name":"Winthrop P. Rockefeller Cancer Institute University of Arkansas for Medical Sciences  Little Rock Arkansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0978-5863","authenticated-orcid":false,"given":"Philip J.","family":"Lupo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Baylor College of Medicine  Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8318-4049","authenticated-orcid":false,"given":"Wendy N.","family":"Nembhard","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Fay W. Boozman College of Public Health University of Arkansas for Medical Sciences  Little Rock Arkansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,7,28]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.125187.111"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu049"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2020.00374"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2022.07.062"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.2500\/aap.2019.40.4205"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-021-01077-7"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/heartjnl-2017-312338"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep19248"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2022.103932"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-3578-9_5"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.00761"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.111.300297"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-019-0159-6"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1047951116002079"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-59696-4_3"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-13-86"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2022.04.035"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI85908"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-22744-6"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1009189"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a036749"},{"volume-title":"Cyanotic heart disease","year":"2023","author":"Ossa Galvis M. 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