Associations between infant sex and DNA methylation across umbilical cord blood, artery, and placenta samples.

{"sci_version": "1.0", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34569420", "kind": "science-record", "revision": 3, "content_hash": "sha256:d3231e8467e17612e7d4d62e41f23f542582efd12c33b1b60d3f7940056a52d9", "created_at": "2026-11-01T17:36:11Z", "updated_at": "2026-11-01T21:26:19Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Associations between infant sex and DNA methylation across umbilical cord blood, artery, and placenta samples.", "doi": "10.1080/15592294.2021.1985300", "pmid": "34569420", "authors": ["Anne K Bozack", "Elena Colicino", "Allan C Just", "Robert O Wright", "Andrea A Baccarelli", "Rosalind J Wright", "Alison G Lee"], "journal": "Epigenetics", "year": 2022, "abstract": "DNA methylation (DNAm) is vulnerable to dysregulation by environmental exposures during epigenetic reprogramming that occurs in embryogenesis. Sexual dimorphism in environmentally induced DNAm dysregulation has been identified and therefore it is important to understand sex-specific DNAm patterns. DNAm at several autosomal sites has been consistently associated with sex in cord blood and placental foetal tissues. However, there is limited research comparing sex-specific DNAm across tissues, particularly differentially methylated regions (DMRs). This study leverages DNAm data measured using the Illumina HumanMethylation450 BeadChip in cord blood (N = 179), placenta (N = 229), and umbilical artery samples (N = 229) in the PRogramming of Intergenerational Stress Mechanisms (PRISM) cohort to identify autosomal DMRs and differentially methylated positions (DMPs). A replication analyses was conducted in an independent cohort (GEO Accession GSE129841). We identified 183, 257, and 419 DMRs and 2119, 2281, and 3405 DMPs (pBonferroni < 0.05) in cord blood, placenta, and artery samples, respectively. Thirty-nine DMRs overlapped in all three tissues, overlapping with genes involved in spermatogenesis (NKAPL, PIWIL2 and AURKC) and X-inactivation (LRIF1). In replication analysis, 85% of DMRs overlapped with those identified in PRISM. Overall, DMRs and DMPs had higher methylation levels among females in cord blood and artery samples, but higher methylation levels among males in placenta samples. Further research is necessary to understand biological mechanisms that contribute to differences in sex-specific DNAm signatures across tissues, as well as to determine if sexual dimorphism in the epigenome impacts response to environmental stressors.", "claims": [{"id": "claim-method", "statement": "We identified 183, 257, and 419 DMRs and 2119, 2281, and 3405 DMPs (pBonferroni < 0.05) in cord blood, placenta, and artery samples, respectively.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34569420", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "We identified 183, 257, and 419 DMRs and 2119, 2281, and 3405 DMPs (pBonferroni < 0.05) in cord blood, placenta, and artery samples, respectively."}], "state": "complete"}, {"id": "claim-data-access", "statement": "A replication analyses was conducted in an independent cohort (GEO Accession GSE129841).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34569420", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "A replication analyses was conducted in an independent cohort (GEO Accession GSE129841)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study identified 183, 257, and 419 DMRs and 2119, 2281, and 3405 DMPs in cord blood, placenta, and artery samples, respectively, with 39 DMRs overlapping across all three tissues and 85% of DMRs overlapping in replication analysis.", "kind": "quantitative", "target": {"value": 85.0, "unit": "per cent", "tolerance": null, "source": "In replication analysis, 85% of DMRs overlapped with those identified in PRISM."}, "evidence": [{"asset": "source:pmid:34569420", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "We identified 183, 257, and 419 DMRs and 2119, 2281, and 3405 DMPs (pBonferroni < 0.05) in cord blood, placenta, and artery samples, respectively."}, {"asset": "source:pmid:34569420", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Thirty-nine DMRs overlapped in all three tissues, overlapping with genes involved in spermatogenesis (NKAPL, PIWIL2 and AURKC) and X–inactivation (LRIF1)."}, {"asset": "source:pmid:34569420", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "In replication analysis, 85% of DMRs overlapped with those identified in PRISM."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The study identified 183, 257, and 419 DMRs and 2119, 2281, and 3405 DMPs in cord blood, placenta, and artery samples, respectively, with 39 DMRs overlapping across all three tissues and 85% of DMRs overlapping in replication analysis.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:34569420"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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