{"doi":"10.1093/aje/kwae254","title":"Epigenome-wide differential methylation and differential variability as predictors of high-grade cervical intraepithelial neoplasia (CIN2+)","abstract":"CpG site methylation patterns have potential to improve differentiation of high-grade screening-detected cervical abnormalities. We assessed CpG differential methylation (DM) and differential variability (DV) in high-grade (CIN2+) vs low-grade (≤ CIN1) lesions. In ≤ CIN1 (n = 117) and CIN2+ (n = 31) samples, cervical sample DNA underwent testing with Illumina HumanMethylation arrays. We assessed DM and DV of CpG methylation M-values among 9 cervical cancer-associated genes. We fit CpG-specific linear models and estimated empirical Bayes standard errors and false discovery rates (FDRs). An exploratory epigenome-wide association study (EWAS) aimed to detect novel DM and DV CpGs (FDR < 0.05) and Gene Ontology (GO) term enrichment. Compared to ≤ CIN1, CIN2+ exhibited greater methylation at CCNA1 cluster 1 (M-value difference 0.24; 95% CI, 0.04-0.43) and RARB cluster 2 (0.16; 95% CI, 0.05-0.28), and lower methylation at CDH1 cluster 1 (-0.15; 95% CI, -0.26 to -0.04). CIN2+ exhibited lower variability at CDH1 cluster 2 (variation difference -0.24; 95% CI, -0.41 to -0.05) and FHIT cluster 1 (-0.30; 95% CI, -0.50 to -0.09). EWAS detected 3534 DM and 270 DV CpGs. Forty-four GO terms were enriched with DM CpGs related to transcriptional, structural, developmental, and neuronal processes. Methylation patterns may help triage screening-detected cervical abnormalities and inform US screening algorithms. This article is part of a Special Collection on Gynecological Cancer.","journal":"American Journal of Epidemiology","year":2024,"id":477322,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9614,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":258281,"name":"Cathrine Hoyo","orcid":"0000-0002-2466-8617","position":1,"is_corresponding":false},{"id":386560,"name":"Misa Graff","orcid":null,"position":2,"is_corresponding":false},{"id":369798,"name":"Nadja A. Vielot","orcid":"0000-0002-9004-0609","position":3,"is_corresponding":false},{"id":367010,"name":"Michael R. Kosorok","orcid":"0000-0002-6070-9738","position":4,"is_corresponding":false},{"id":453040,"name":"Wendy R. Brewster","orcid":"0000-0001-6150-3160","position":5,"is_corresponding":false},{"id":270428,"name":"Rachel L. Maguire","orcid":"0000-0001-6421-2545","position":6,"is_corresponding":false},{"id":270429,"name":"Susan K. Murphy","orcid":"0000-0001-8298-7272","position":7,"is_corresponding":false},{"id":733911,"name":"Belinda Nedjai","orcid":"0000-0001-8711-4577","position":8,"is_corresponding":false},{"id":1113603,"name":"Efthymios Ladoukakis","orcid":"0000-0002-4807-1292","position":9,"is_corresponding":false},{"id":11361,"name":"Kari E. North","orcid":"0000-0002-8903-0366","position":10,"is_corresponding":false},{"id":369802,"name":"Jennifer S. Smith","orcid":"0000-0002-1256-0422","position":11,"is_corresponding":false},{"id":944463,"name":"Alexandra Bukowski","orcid":"0000-0001-7634-7340","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-19T02:06:33.741984Z","pmid":"39117569","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}