{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T06:44:56Z","timestamp":1784616296382,"version":"3.55.0"},"reference-count":52,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,10]],"date-time":"2023-02-10T00:00:00Z","timestamp":1675987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2019s Horizon 2020 research and innovation program","award":["765274"],"award-info":[{"award-number":["765274"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>In this study, we attempted to find genetic variants affecting gene expression (eQTL = expression Quantitative Trait Loci) in the human placenta in normal and pathological situations. The analysis of gene expression in placental diseases (Pre-eclampsia and Intra-Uterine Growth Restriction) is hindered by the fact that diseased placental tissue samples are generally taken at earlier gestations compared to control samples. The difference in gestational age is considered a major confounding factor in the transcriptome regulation of the placenta. To alleviate this significant problem, we propose here a novel approach to pinpoint disease-specific cis-eQTLs. By statistical correction for gestational age at sampling as well as other confounding\/surrogate variables systematically searched and identified, we found 43 e-genes for which proximal SNPs influence expression level. Then, we performed the analysis again, removing the disease status from the covariates, and we identified 54 e-genes, 16 of which are identified de novo and, thus, possibly related to placental disease. We found a highly significant overlap with previous studies for the list of 43 e-genes, validating our methodology and findings. Among the 16 disease-specific e-genes, several are intrinsic to trophoblast biology and, therefore, constitute novel targets of interest to better characterize placental pathology and its varied clinical consequences. The approach that we used may also be applied to the study of other human diseases where confounding factors have hampered a better understanding of the pathology.<\/jats:p>","DOI":"10.3390\/cells12040578","type":"journal-article","created":{"date-parts":[[2023,2,13]],"date-time":"2023-02-13T04:32:58Z","timestamp":1676262778000},"page":"578","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Pan-Genomic Regulation of Gene Expression in Normal and Pathological Human Placentas"],"prefix":"10.3390","volume":"12","author":[{"given":"Clara","family":"Apicella","sequence":"first","affiliation":[{"name":"Team \u2018From Gametes to Birth\u2019, Institut Cochin, U1016 INSERM, UMR 8104 CNRS, Paris-Descartes University, 75014 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camino S. M.","family":"Ruano","sequence":"additional","affiliation":[{"name":"Team \u2018From Gametes to Birth\u2019, Institut Cochin, U1016 INSERM, UMR 8104 CNRS, Paris-Descartes University, 75014 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5531-4301","authenticated-orcid":false,"given":"Basky","family":"Thilaganathan","sequence":"additional","affiliation":[{"name":"Fetal Medicine Unit, St George\u2019s University Hospitals NHS Foundation Trust, London SW17 0RE, UK"},{"name":"Vascular Biology Research Centre, Molecular and Clinical Sciences Research Institute, St George\u2019s University of London, London SW17 0RE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2802-7670","authenticated-orcid":false,"given":"Asma","family":"Khalil","sequence":"additional","affiliation":[{"name":"Fetal Medicine Unit, St George\u2019s University Hospitals NHS Foundation Trust, London SW17 0RE, UK"},{"name":"Vascular Biology Research Centre, Molecular and Clinical Sciences Research Institute, St George\u2019s University of London, London SW17 0RE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3991-9308","authenticated-orcid":false,"given":"Veronica","family":"Giorgione","sequence":"additional","affiliation":[{"name":"Fetal Medicine Unit, St George\u2019s University Hospitals NHS Foundation Trust, London SW17 0RE, UK"},{"name":"Vascular Biology Research Centre, Molecular and Clinical Sciences Research Institute, St George\u2019s University of London, London SW17 0RE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00e9raldine","family":"Gascoin","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Angers University Hospital, F-49000 Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4482-9710","authenticated-orcid":false,"given":"Louis","family":"Marcellin","sequence":"additional","affiliation":[{"name":"Department of Gynaecology, Obstetrics and Reproductive Medicine, Centre Hospitalier Universitaire (CHU) Cochin Facult\u00e9 de M\u00e9decine, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), H\u00f4pitaux Universitaires Paris Centre (HUPC), Universit\u00e9 de Paris, 138 Boulevard de Port-Royal, 75014 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassandra","family":"Gaspar","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Inserm, UMS Production et Analyse des donn\u00e9es en Sciences de la vie et en Sant\u00e9, PASS, Plateforme Post-g\u00e9nomique de la Piti\u00e9-Salp\u00eatri\u00e8re, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Jacques","sequence":"additional","affiliation":[{"name":"Team \u2018From Gametes to Birth\u2019, Institut Cochin, U1016 INSERM, UMR 8104 CNRS, Paris-Descartes University, 75014 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0274-819X","authenticated-orcid":false,"given":"Colin E.","family":"Murdoch","sequence":"additional","affiliation":[{"name":"Systems Medicine, School of Medicine, University of Dundee, Dundee DD1 9SY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Miralles","sequence":"additional","affiliation":[{"name":"Team \u2018From Gametes to Birth\u2019, Institut Cochin, U1016 INSERM, UMR 8104 CNRS, Paris-Descartes University, 75014 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3677-2024","authenticated-orcid":false,"given":"C\u00e9line","family":"M\u00e9hats","sequence":"additional","affiliation":[{"name":"Team \u2018From Gametes to Birth\u2019, Institut Cochin, U1016 INSERM, UMR 8104 CNRS, Paris-Descartes University, 75014 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1915-0717","authenticated-orcid":false,"given":"Daniel","family":"Vaiman","sequence":"additional","affiliation":[{"name":"Team \u2018From Gametes to Birth\u2019, Institut Cochin, U1016 INSERM, UMR 8104 CNRS, Paris-Descartes University, 75014 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"E6566","DOI":"10.1073\/pnas.1701129114","article-title":"Embryo implantation evolved from an ancestral inflammatory attachment reaction","volume":"114","author":"Griffith","year":"2017","journal-title":"Proc. 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