{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T23:40:20Z","timestamp":1794008420948,"version":"4.8.0"},"reference-count":98,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,12,11]],"date-time":"2021-12-11T00:00:00Z","timestamp":1639180800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,12,11]],"date-time":"2021-12-11T00:00:00Z","timestamp":1639180800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000024","name":"canadian institutes of health research","doi-asserted-by":"publisher","award":["MOP 123319"],"award-info":[{"award-number":["MOP 123319"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000182","name":"worksafebc","doi-asserted-by":"publisher","award":["RG2011-OG07"],"award-info":[{"award-number":["RG2011-OG07"]}],"id":[{"id":"10.13039\/501100000182","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Epigenetics &amp; Chromatin"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Understanding the molecular basis of susceptibility factors to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a global health imperative. It is well-established that males are more likely to acquire SARS-CoV-2 infection and exhibit more severe outcomes. Similarly, exposure to air pollutants and pre-existing respiratory chronic conditions, such as asthma and chronic obstructive respiratory disease (COPD) confer an increased risk to coronavirus disease 2019 (COVID-19).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We investigated molecular patterns associated with risk factors in 398 candidate genes relevant to COVID-19 biology. To accomplish this, we downloaded DNA methylation and gene expression data sets from publicly available repositories (GEO and GTEx Portal) and utilized data from an empirical controlled human exposure study conducted by our team.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      First, we observed sex-biased DNA methylation patterns in autosomal immune genes, such as\n                      <jats:italic>NLRP2<\/jats:italic>\n                      ,\n                      <jats:italic>TLE1<\/jats:italic>\n                      ,\n                      <jats:italic>GPX1<\/jats:italic>\n                      , and\n                      <jats:italic>ARRB2<\/jats:italic>\n                      (FDR\u2009&lt;\u20090.05, magnitude of DNA methylation difference \u0394\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2009&gt;\u20090.05). Second, our analysis on the X-linked genes identified sex associated DNA methylation profiles in genes, such as\n                      <jats:italic>ACE2<\/jats:italic>\n                      ,\n                      <jats:italic>CA5B<\/jats:italic>\n                      , and\n                      <jats:italic>HS6ST2<\/jats:italic>\n                      (FDR\u2009&lt;\u20090.05, \u0394\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2009&gt;\u20090.05). These associations were observed across multiple respiratory tissues (lung, nasal epithelia, airway epithelia, and bronchoalveolar lavage) and in whole blood. Some of these genes, such as\n                      <jats:italic>NLRP2<\/jats:italic>\n                      and\n                      <jats:italic>CA5B<\/jats:italic>\n                      , also exhibited sex-biased gene expression patterns. In addition, we found differential DNA methylation patterns by COVID-19 status for genes, such as\n                      <jats:italic>NLRP2<\/jats:italic>\n                      and\n                      <jats:italic>ACE2<\/jats:italic>\n                      in an exploratory analysis of an empirical data set reporting on human COVID-9 infections. Third, we identified modest DNA methylation changes in CpGs associated with\n                      <jats:italic>PRIM2<\/jats:italic>\n                      and\n                      <jats:italic>TATDN1<\/jats:italic>\n                      (FDR\u2009&lt;\u20090.1, \u0394\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2009&gt;\u20090.05) in response to particle-depleted diesel exhaust in bronchoalveolar lavage. Finally, we captured a DNA methylation signature associated with COPD diagnosis in a gene involved in nicotine dependence (\n                      <jats:italic>COMT<\/jats:italic>\n                      ) (FDR\u2009&lt;\u20090.1, \u0394\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2009&gt;\u20090.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our findings on sex differences might be of clinical relevance given that they revealed molecular associations of sex-biased differences in COVID-19. Specifically, our results hinted at a potentially exaggerated immune response in males linked to autosomal genes, such as\n                      <jats:italic>NLRP2.<\/jats:italic>\n                      In contrast, our findings at X-linked loci such as\n                      <jats:italic>ACE2<\/jats:italic>\n                      suggested a potentially distinct DNA methylation pattern in females that may interact with its mRNA expression and inactivation status. We also found tissue-specific DNA methylation differences in response to particulate exposure potentially capturing a nitrogen dioxide (NO\n                      <jats:sub>2<\/jats:sub>\n                      ) effect\u2014a contributor to COVID-19 susceptibility. While we identified a molecular signature associated with COPD, all COPD-affected individuals were smokers, which may either reflect an association with the disease, smoking, or may highlight a compounded effect of these two risk factors in COVID-19. Overall, our findings point towards a molecular basis of variation in susceptibility factors that may partly explain disparities in the risk for SARS-CoV-2 infection.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13072-021-00428-1","type":"journal-article","created":{"date-parts":[[2021,12,11]],"date-time":"2021-12-11T15:02:28Z","timestamp":1639234948000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Risk-focused differences in molecular processes implicated in SARS-CoV-2 infection: corollaries in DNA methylation and gene expression"],"prefix":"10.1186","volume":"14","author":[{"given":"Chaini","family":"Konwar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Asiimwe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy M.","family":"Inkster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah M.","family":"Merrill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gian L.","family":"Negri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria J.","family":"Aristizabal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher F.","family":"Rider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie L.","family":"MacIsaac","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Carlsten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4140-1743","authenticated-orcid":false,"given":"Michael S.","family":"Kobor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,12,11]]},"reference":[{"issue":"11","key":"428_CR1","doi-asserted-by":"publisher","first-page":"1436","DOI":"10.1001\/jamainternmed.2020.3596","volume":"180","author":"S Gupta","year":"2020","unstructured":"Gupta S, Hayek SS, Wang W, Chan L, Mathews KS, Melamed ML, et al. Factors associated with death in critically ill patients with coronavirus disease 2019 in the US. JAMA Intern Med. 2020;180(11):1436.","journal-title":"JAMA Intern Med"},{"issue":"10","key":"428_CR2","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.1001\/jamainternmed.2020.3539","volume":"180","author":"G Grasselli","year":"2020","unstructured":"Grasselli G, Greco M, Zanella A, Albano G, Antonelli M, Bellani G, et al. Risk factors associated with mortality among patients with COVID-19 in intensive care units in Lombardy, Italy. JAMA Intern Med. 2020;180(10):1345.","journal-title":"JAMA Intern Med"},{"issue":"7821","key":"428_CR3","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1038\/s41586-020-2521-4","volume":"584","author":"EJ Williamson","year":"2020","unstructured":"Williamson EJ, Walker AJ, Bhaskaran K, Bacon S, Bates C, Morton CE, et al. Factors associated with COVID-19-related death using OpenSAFELY. Nature. 2020;584(7821):430\u20136.","journal-title":"Nature"},{"issue":"8","key":"428_CR4","doi-asserted-by":"publisher","first-page":"e1003","DOI":"10.1016\/S2214-109X(20)30264-3","volume":"8","author":"A Clark","year":"2020","unstructured":"Clark A, Jit M, Warren-Gash C, Guthrie B, Wang HHX, Mercer SW, et al. Global, regional, and national estimates of the population at increased risk of severe COVID-19 due to underlying health conditions in 2020: a modelling study. Lancet Glob Health. 2020;8(8):e1003\u201317.","journal-title":"Lancet Glob Health"},{"key":"428_CR5","first-page":"12","volume":"1","author":"G Rabbani","year":"2021","unstructured":"Rabbani G, Shariful Islam SM, Rahman MA, Amin N, Marzan B, Robin RC, et al. Pre-existing COPD is associated with an increased risk of mortality and severity in COVID-19: a rapid systematic review and meta-analysis. Expert Rev Respir Med. 2021;1:12.","journal-title":"Expert Rev Respir Med"},{"issue":"3","key":"428_CR6","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1093\/aje\/kwh056","volume":"159","author":"J Karlberg","year":"2004","unstructured":"Karlberg J. Do men have a higher case fatality rate of severe acute respiratory syndrome than women do? Am J Epidemiol. 2004;159(3):229\u201331.","journal-title":"Am J Epidemiol"},{"key":"428_CR7","unstructured":"Global Health 50\/50. The sex, gender and COVID-19 project. 2020. https:\/\/globalhealth5050.org\/the-sex-gender-and-covid-19-project\/. Accessed 12 Jan 2021."},{"issue":"7","key":"428_CR8","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1038\/s41577-020-0348-8","volume":"20","author":"EP Scully","year":"2020","unstructured":"Scully EP, Haverfield J, Ursin RL, Tannenbaum C, Klein SL. Considering how biological sex impacts immune responses and COVID-19 outcomes. Nat Rev Immunol. 2020;20(7):442\u20137.","journal-title":"Nat Rev Immunol"},{"issue":"10223","key":"428_CR9","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1016\/S0140-6736(20)30211-7","volume":"395","author":"N Chen","year":"2020","unstructured":"Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507\u201313.","journal-title":"Lancet"},{"issue":"18","key":"428_CR10","doi-asserted-by":"publisher","first-page":"1708","DOI":"10.1056\/NEJMoa2002032","volume":"382","author":"W Guan","year":"2020","unstructured":"Guan W, Ni Z, Hu Y, Liang W, Ou C, He J, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382(18):1708\u201320.","journal-title":"N Engl J Med"},{"key":"428_CR11","unstructured":"NYC Health. COVID-19: Data. 2020. https:\/\/www1.nyc.gov\/site\/doh\/covid\/covid-19-data.page. Accessed 2 Feb 2021."},{"issue":"1","key":"428_CR12","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1186\/s13293-020-00304-9","volume":"11","author":"C Gebhard","year":"2020","unstructured":"Gebhard C, Regitz-Zagrosek V, Neuhauser HK, Morgan R, Klein SL. Impact of sex and gender on COVID-19 outcomes in Europe. Biol Sex Differ. 2020;11(1):29.","journal-title":"Biol Sex Differ"},{"issue":"4","key":"428_CR13","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1016\/j.bbi.2007.10.005","volume":"22","author":"MF Hannah","year":"2008","unstructured":"Hannah MF, Bajic VB, Klein SL. Sex differences in the recognition of and innate antiviral responses to Seoul virus in Norway rats. Brain, Behav Immun. 2008;22(4):503\u201316.","journal-title":"Brain, Behav Immun"},{"issue":"10","key":"428_CR14","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1038\/nri.2016.90","volume":"16","author":"SL Klein","year":"2016","unstructured":"Klein SL, Flanagan KL. Sex differences in immune responses. Nat Rev Immunol. 2016;16(10):626\u201338.","journal-title":"Nat Rev Immunol"},{"key":"428_CR15","doi-asserted-by":"crossref","unstructured":"Yale IMPACT Research Team, Takahashi T, Ellingson MK, Wong P, Israelow B, Lucas C, et al. Sex differences in immune responses that underlie COVID-19 disease outcomes. Nature. 2020;588(7837):315\u201320.","DOI":"10.1038\/s41586-020-2700-3"},{"issue":"1","key":"428_CR16","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/s13072-016-0079-z","volume":"9","author":"S Wallner","year":"2016","unstructured":"Wallner S, Schr\u00f6der C, Leit\u00e3o E, Berulava T, Haak C, Bei\u00dfer D, et al. Epigenetic dynamics of monocyte-to-macrophage differentiation. Epigenetics Chromatin. 2016;9(1):33.","journal-title":"Epigenetics Chromatin"},{"issue":"1","key":"428_CR17","doi-asserted-by":"publisher","first-page":"110","DOI":"10.3390\/genes11010110","volume":"11","author":"C de la Calle-Fabregat","year":"2020","unstructured":"de la Calle-Fabregat C, Morante-Palacios O, Ballestar E. Understanding the relevance of DNA methylation changes in immune differentiation and disease. Genes. 2020;11(1):110.","journal-title":"Genes"},{"issue":"6","key":"428_CR18","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1016\/j.tig.2016.03.007","volume":"32","author":"BP Balaton","year":"2016","unstructured":"Balaton BP, Brown CJ. Escape artists of the x chromosome. Trends Genet. 2016;32(6):348\u201359.","journal-title":"Trends Genet"},{"issue":"8","key":"428_CR19","doi-asserted-by":"publisher","first-page":"746","DOI":"10.1002\/bies.201400032","volume":"36","author":"SB Peeters","year":"2014","unstructured":"Peeters SB, Cotton AM, Brown CJ. Variable escape from X-chromosome inactivation: Identifying factors that tip the scales towards expression. BioEssays. 2014;36(8):746\u201356.","journal-title":"BioEssays"},{"issue":"7031","key":"428_CR20","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1038\/nature03479","volume":"434","author":"L Carrel","year":"2005","unstructured":"Carrel L, Willard HF. X-inactivation profile reveals extensive variability in X-linked gene expression in females. Nature. 2005;434(7031):400\u20134.","journal-title":"Nature"},{"issue":"2\u20133","key":"428_CR21","doi-asserted-by":"publisher","first-page":"J187","DOI":"10.1016\/j.jaut.2011.11.012","volume":"38","author":"I Bianchi","year":"2012","unstructured":"Bianchi I, Lleo A, Gershwin ME, Invernizzi P. The X chromosome and immune associated genes. J Autoimmun. 2012;38(2\u20133):J187\u201392.","journal-title":"J Autoimmun"},{"issue":"4","key":"428_CR22","doi-asserted-by":"publisher","first-page":"2060","DOI":"10.4049\/jimmunol.167.4.2060","volume":"167","author":"SM Liva","year":"2001","unstructured":"Liva SM, Voskuhl RR. Testosterone Acts Directly on CD4 + T Lymphocytes to Increase IL-10 Production. J Immunol. 2001;167(4):2060\u20137.","journal-title":"J Immunol"},{"issue":"1","key":"428_CR23","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1186\/s12863-018-0703-y","volume":"19","author":"R Arathimos","year":"2018","unstructured":"Arathimos R, Sharp GC, Granell R, Tilling K, Relton CL. Associations of sex hormone-binding globulin and testosterone with genome-wide DNA methylation. BMC Genet. 2018;19(1):113.","journal-title":"BMC Genet"},{"issue":"1","key":"428_CR24","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1186\/s13072-015-0035-3","volume":"8","author":"P Singmann","year":"2015","unstructured":"Singmann P, Shem-Tov D, Wahl S, Grallert H, Fiorito G, Shin S-Y, et al. Characterization of whole-genome autosomal differences of DNA methylation between men and women. Epigenetics Chromatin. 2015;8(1):43.","journal-title":"Epigenetics Chromatin"},{"issue":"10","key":"428_CR25","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1080\/15592294.2015.1084462","volume":"10","author":"S Mamrut","year":"2015","unstructured":"Mamrut S, Avidan N, Staun-Ram E, Ginzburg E, Truffault F, Berrih-Aknin S, et al. Integrative analysis of methylome and transcriptome in human blood identifies extensive sex- and immune cell-specific differentially methylated regions. Epigenetics. 2015;10(10):943\u201357.","journal-title":"Epigenetics"},{"issue":"1","key":"428_CR26","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1038\/s41467-020-14396-9","volume":"11","author":"EJ M\u00e1rquez","year":"2020","unstructured":"M\u00e1rquez EJ, Chung C, Marches R, Rossi RJ, Nehar-Belaid D, Eroglu A, et al. Sexual-dimorphism in human immune system aging. Nat Commun. 2020;11(1):751.","journal-title":"Nat Commun"},{"issue":"3","key":"428_CR27","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1016\/j.chest.2015.12.018","volume":"149","author":"JL Simpson","year":"2016","unstructured":"Simpson JL, Carroll M, Yang IA, Reynolds PN, Hodge S, James AL, et al. Reduced Antiviral Interferon Production in Poorly Controlled Asthma Is Associated With Neutrophilic Inflammation and High-Dose Inhaled Corticosteroids. Chest. 2016;149(3):704\u201313.","journal-title":"Chest"},{"issue":"4","key":"428_CR28","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1016\/j.jcv.2004.07.006","volume":"31","author":"N Lee","year":"2004","unstructured":"Lee N, Allen Chan KC, Hui DS, Ng EKO, Wu A, Chiu RWK, et al. Effects of early corticosteroid treatment on plasma SARS-associated Coronavirus RNA concentrations in adult patients. J Clin Virol. 2004;31(4):304\u20139.","journal-title":"J Clin Virol"},{"issue":"2","key":"428_CR29","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1016\/j.jaci.2020.06.010","volume":"146","author":"KD Chhiba","year":"2020","unstructured":"Chhiba KD, Patel GB, Vu THT, Chen MM, Guo A, Kudlaty E, et al. Prevalence and characterization of asthma in hospitalized and nonhospitalized patients with COVID-19. J Allergy Clin Immunol. 2020;146(2):307-314.e4.","journal-title":"J Allergy Clin Immunol"},{"issue":"1","key":"428_CR30","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1186\/s13148-018-0464-5","volume":"10","author":"RL Clifford","year":"2018","unstructured":"Clifford RL, Fishbane N, Patel J, MacIsaac JL, McEwen LM, Fisher AJ, et al. Altered DNA methylation is associated with aberrant gene expression in parenchymal but not airway fibroblasts isolated from individuals with COPD. Clin Epigenet. 2018;10(1):32.","journal-title":"Clin Epigenet"},{"issue":"1","key":"428_CR31","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.jaci.2015.01.025","volume":"136","author":"IV Yang","year":"2015","unstructured":"Yang IV, Pedersen BS, Liu A, O\u2019Connor GT, Teach SJ, Kattan M, et al. DNA methylation and childhood asthma in the inner city. J Allergy Clin Immunol. 2015;136(1):69\u201380.","journal-title":"J Allergy Clin Immunol"},{"issue":"45","key":"428_CR32","doi-asserted-by":"publisher","first-page":"eabd4049","DOI":"10.1126\/sciadv.abd4049","volume":"6","author":"X Wu","year":"2020","unstructured":"Wu X, Nethery RC, Sabath MB, Braun D, Dominici F. Air pollution and COVID-19 mortality in the United States: Strengths and limitations of an ecological regression analysis. Sci Adv. 2020;6(45):eabd4049.","journal-title":"Sci Adv"},{"key":"428_CR33","doi-asserted-by":"publisher","unstructured":"Andr\u00e9e BPJ. Incidence of COVID-19 and connections with air pollution exposure: evidence from the Netherlands. http:\/\/medrxiv.org\/lookup\/doi\/https:\/\/doi.org\/10.1101\/2020.04.27.20081562 (2020). Accessed 23 Mar 2021.","DOI":"10.1101\/2020.04.27.20081562"},{"key":"428_CR34","doi-asserted-by":"publisher","first-page":"114465","DOI":"10.1016\/j.envpol.2020.114465","volume":"261","author":"E Conticini","year":"2020","unstructured":"Conticini E, Frediani B, Caro D. Can atmospheric pollution be considered a co-factor in extremely high level of SARS-CoV-2 lethality in Northern Italy? Environ Pollut. 2020;261:114465.","journal-title":"Environ Pollut"},{"key":"428_CR35","doi-asserted-by":"publisher","first-page":"115859","DOI":"10.1016\/j.envpol.2020.115859","volume":"268","author":"M Travaglio","year":"2021","unstructured":"Travaglio M, Yu Y, Popovic R, Selley L, Leal NS, Martins LM. Links between air pollution and COVID-19 in England. Environ Pollut. 2021;268:115859.","journal-title":"Environ Pollut"},{"issue":"1","key":"428_CR36","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/j.jaci.2016.03.046","volume":"139","author":"RL Clifford","year":"2017","unstructured":"Clifford RL, Jones MJ, MacIsaac JL, McEwen LM, Goodman SJ, Mostafavi S, et al. Inhalation of diesel exhaust and allergen alters human bronchial epithelium DNA methylation. J Allergy Clin Immunol. 2017;139(1):112\u201321.","journal-title":"J Allergy Clin Immunol"},{"key":"428_CR37","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/j.envint.2017.08.006","volume":"108","author":"M Plusquin","year":"2017","unstructured":"Plusquin M, Guida F, Polidoro S, Vermeulen R, Raaschou-Nielsen O, Campanella G, et al. DNA methylation and exposure to ambient air pollution in two prospective cohorts. Environ Int. 2017;108:127\u201336.","journal-title":"Environ Int"},{"issue":"1","key":"428_CR38","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1186\/s13148-019-0713-2","volume":"11","author":"CF Rider","year":"2019","unstructured":"Rider CF, Carlsten C. Air pollution and DNA methylation: effects of exposure in humans. Clin Epigenet. 2019;11(1):131.","journal-title":"Clin Epigenet"},{"issue":"5","key":"428_CR39","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1164\/rccm.201809-1657OC","volume":"200","author":"DJ Wooding","year":"2019","unstructured":"Wooding DJ, Ryu MH, H\u00fcls A, Lee AD, Lin DTS, Rider CF, et al. Particle depletion does not remediate acute effects of traffic-related air pollution and allergen. A randomized, double-blind crossover study. Am J Respir Crit Care Med. 2019;200(5):565\u201374.","journal-title":"Am J Respir Crit Care Med"},{"issue":"7798","key":"428_CR40","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1038\/s41586-020-2012-7","volume":"579","author":"P Zhou","year":"2020","unstructured":"Zhou P, Yang X-L, Wang X-G, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270\u20133.","journal-title":"Nature"},{"issue":"2","key":"428_CR41","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/j.cell.2020.02.052","volume":"181","author":"M Hoffmann","year":"2020","unstructured":"Hoffmann M, Kleine-Weber H, Schroeder S, Kr\u00fcger N, Herrler T, Erichsen S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181(2):271-280.e8.","journal-title":"Cell"},{"issue":"1","key":"428_CR42","doi-asserted-by":"publisher","first-page":"1620","DOI":"10.1038\/s41467-020-15562-9","volume":"11","author":"X Ou","year":"2020","unstructured":"Ou X, Liu Y, Lei X, Li P, Mi D, Ren L, et al. Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Nat Commun. 2020;11(1):1620.","journal-title":"Nat Commun"},{"issue":"6","key":"428_CR43","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1093\/ndt\/gfaa093","volume":"35","author":"V Palau","year":"2020","unstructured":"Palau V, Riera M, Soler MJ. ADAM17 inhibition may exert a protective effect on COVID-19. Nephrol Dial Transplant. 2020;35(6):1071\u20132.","journal-title":"Nephrol Dial Transplant"},{"issue":"12","key":"428_CR44","doi-asserted-by":"publisher","first-page":"e1008461","DOI":"10.1371\/journal.pcbi.1008461","volume":"16","author":"P Padmanabhan","year":"2020","unstructured":"Padmanabhan P, Desikan R, Dixit NM. Targeting TMPRSS2 and Cathepsin B\/L together may be synergistic against SARS-CoV-2 infection. PLoS Comput Biol. 2020;16(12):e1008461.","journal-title":"PLoS Comput Biol"},{"issue":"10","key":"428_CR45","first-page":"4046","volume":"198","author":"R Channappanavar","year":"2017","unstructured":"Channappanavar R, Fett C, Mack M, Ten Eyck PP, Meyerholz DK, Perlman S. Sex-based differences in susceptibility to severe acute respiratory syndrome coronavirus infection. JI. 2017;198(10):4046\u201353.","journal-title":"JI"},{"issue":"4\u20135","key":"428_CR46","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1016\/j.micinf.2020.04.009","volume":"22","author":"MA Moreno-Eutimio","year":"2020","unstructured":"Moreno-Eutimio MA, L\u00f3pez-Mac\u00edas C, Pastelin-Palacios R. Bioinformatic analysis and identification of single-stranded RNA sequences recognized by TLR7\/8 in the SARS-CoV-2, SARS-CoV, and MERS-CoV genomes. Microbes Infect. 2020;22(4\u20135):226\u20139.","journal-title":"Microbes Infect"},{"issue":"7816","key":"428_CR47","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1038\/s41586-020-2286-9","volume":"583","author":"DE Gordon","year":"2020","unstructured":"Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, et al. A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature. 2020;583(7816):459\u201368.","journal-title":"Nature"},{"issue":"9","key":"428_CR48","doi-asserted-by":"publisher","first-page":"e3000849","DOI":"10.1371\/journal.pbio.3000849","volume":"18","author":"NAP Lieberman","year":"2020","unstructured":"Lieberman NAP, Peddu V, Xie H, Shrestha L, Huang M-L, Mears MC, et al. In vivo antiviral host transcriptional response to SARS-CoV-2 by viral load, sex, and age. PLoS Biol. 2020;18(9):e3000849.","journal-title":"PLoS Biol"},{"issue":"19","key":"428_CR49","doi-asserted-by":"publisher","first-page":"3544","DOI":"10.1093\/hmg\/ddp299","volume":"18","author":"AM Cotton","year":"2009","unstructured":"Cotton AM, Avila L, Penaherrera MS, Affleck JG, Robinson WP, Brown CJ. Inactive X chromosome-specific reduction in placental DNA methylation. Hum Mol Genet. 2009;18(19):3544\u201352.","journal-title":"Hum Mol Genet"},{"issue":"2","key":"428_CR50","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1007\/s00439-011-1007-8","volume":"130","author":"AM Cotton","year":"2011","unstructured":"Cotton AM, Lam L, Affleck JG, Wilson IM, Pe\u00f1aherrera MS, McFadden DE, et al. Chromosome-wide DNA methylation analysis predicts human tissue-specific X inactivation. Hum Genet. 2011;130(2):187\u2013201.","journal-title":"Hum Genet"},{"issue":"3","key":"428_CR51","doi-asserted-by":"publisher","first-page":"E488","DOI":"10.1073\/pnas.1714765115","volume":"115","author":"B Piasecka","year":"2018","unstructured":"Piasecka B, Duffy D, Urrutia A, Quach H, Patin E, Posseme C, et al. Distinctive roles of age, sex, and genetics in shaping transcriptional variation of human immune responses to microbial challenges. Proc Natl Acad Sci USA. 2018;115(3):E488\u201397.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"12","key":"428_CR52","doi-asserted-by":"publisher","first-page":"1801","DOI":"10.1101\/gr.192005.115","volume":"25","author":"A Pacis","year":"2015","unstructured":"Pacis A, Tailleux L, Morin AM, Lambourne J, MacIsaac JL, Yotova V, et al. Bacterial infection remodels the DNA methylation landscape of human dendritic cells. Genome Res. 2015;25(12):1801\u201311.","journal-title":"Genome Res"},{"issue":"2","key":"428_CR53","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1128\/MMBR.00061-14","volume":"79","author":"SR Paludan","year":"2015","unstructured":"Paludan SR. Activation and Regulation of DNA-Driven Immune Responses. Microbiol Mol Biol Rev. 2015;79(2):225\u201341.","journal-title":"Microbiol Mol Biol Rev"},{"issue":"6","key":"428_CR54","doi-asserted-by":"publisher","first-page":"1528","DOI":"10.1093\/hmg\/ddu564","volume":"24","author":"AM Cotton","year":"2015","unstructured":"Cotton AM, Price EM, Jones MJ, Balaton BP, Kobor MS, Brown CJ. Landscape of DNA methylation on the X chromosome reflects CpG density, functional chromatin state and X-chromosome inactivation. Hum Mol Genet. 2015;24(6):1528\u201339.","journal-title":"Hum Mol Genet"},{"issue":"2","key":"428_CR55","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1002\/ajmg.c.31800","volume":"184","author":"MJ Navarro-Cobos","year":"2020","unstructured":"Navarro-Cobos MJ, Balaton BP, Brown CJ. Genes that escape from X-chromosome inactivation: Potential contributors to Klinefelter syndrome. Am J Med Genet. 2020;184(2):226\u201338.","journal-title":"Am J Med Genet"},{"issue":"1","key":"428_CR56","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1186\/s13293-015-0053-7","volume":"6","author":"BP Balaton","year":"2015","unstructured":"Balaton BP, Cotton AM, Brown CJ. Derivation of consensus inactivation status for X-linked genes from genome-wide studies. Biol Sex Differ. 2015;6(1):35.","journal-title":"Biol Sex Differ"},{"issue":"11","key":"428_CR57","doi-asserted-by":"publisher","first-page":"1817","DOI":"10.1002\/eji.201847589","volume":"48","author":"Y Yang","year":"2018","unstructured":"Yang Y, Lang X, Sun S, Gao C, Hu J, Ding S, et al. NLRP2 negatively regulates antiviral immunity by interacting with TBK1. Eur J Immunol. 2018;48(11):1817\u201325.","journal-title":"Eur J Immunol"},{"issue":"4","key":"428_CR58","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1093\/biolre\/iox009","volume":"96","author":"T Tilburgs","year":"2017","unstructured":"Tilburgs T, Meissner TB, Ferreira LMR, Mulder A, Musunuru K, Ye J, et al. NLRP2 is a suppressor of NF-\u0199B signaling and HLA-C expression in human trophoblasts\u2020,\u2021. Biol Reprod. 2017;96(4):831\u201342.","journal-title":"Biol Reprod"},{"issue":"50","key":"428_CR59","doi-asserted-by":"publisher","first-page":"51897","DOI":"10.1074\/jbc.M406741200","volume":"279","author":"JM Bruey","year":"2004","unstructured":"Bruey JM, Bruey-Sedano N, Newman R, Chandler S, Stehlik C, Reed JC. PAN1\/NALP2\/PYPAF2, an inducible inflammatory mediator that regulates NF-\u03baB and caspase-1 activation in macrophages. J Biol Chem. 2004;279(50):51897\u2013907.","journal-title":"J Biol Chem"},{"issue":"6","key":"428_CR60","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1016\/j.chom.2020.04.017","volume":"27","author":"Z Zhou","year":"2020","unstructured":"Zhou Z, Ren L, Zhang L, Zhong J, Xiao Y, Jia Z, et al. Heightened innate immune responses in the respiratory tract of COVID-19 patients. Cell Host Microbe. 2020;27(6):883-890.e2.","journal-title":"Cell Host Microbe"},{"issue":"10223","key":"428_CR61","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/S0140-6736(20)30183-5","volume":"395","author":"C Huang","year":"2020","unstructured":"Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan. China Lancet. 2020;395(10223):497\u2013506.","journal-title":"China Lancet"},{"key":"428_CR62","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.cytogfr.2020.05.003","volume":"53","author":"F Coperchini","year":"2020","unstructured":"Coperchini F, Chiovato L, Croce L, Magri F, Rotondi M. The cytokine storm in COVID-19: An overview of the involvement of the chemokine\/chemokine-receptor system. Cytokine Growth Factor Rev. 2020;53:25\u201332.","journal-title":"Cytokine Growth Factor Rev"},{"issue":"7","key":"428_CR63","doi-asserted-by":"publisher","first-page":"1961","DOI":"10.1016\/j.celrep.2019.10.019","volume":"29","author":"E Bongen","year":"2019","unstructured":"Bongen E, Lucian H, Khatri A, Fragiadakis GK, Bjornson ZB, Nolan GP, et al. Sex differences in the blood transcriptome identify robust changes in immune cell proportions with aging and influenza infection. Cell Rep. 2019;29(7):1961-1973.e4.","journal-title":"Cell Rep"},{"issue":"9","key":"428_CR64","doi-asserted-by":"publisher","first-page":"3179","DOI":"10.3390\/ijms21093179","volume":"21","author":"Y-S Chang","year":"2020","unstructured":"Chang Y-S, Ko B-H, Ju J-C, Chang H-H, Huang S-H, Lin C-W. SARS Unique Domain (SUD) of severe acute respiratory syndrome coronavirus induces NLRP3 inflammasome-dependent CXCL10-mediated pulmonary inflammation. IJMS. 2020;21(9):3179.","journal-title":"IJMS"},{"issue":"1","key":"428_CR65","doi-asserted-by":"publisher","first-page":"17600","DOI":"10.1038\/s41598-019-54051-y","volume":"9","author":"CX Yang","year":"2019","unstructured":"Yang CX, Shi H, Ding I, Milne S, Hernandez Cordero AI, Yang CWT, et al. Widespread sexual dimorphism in the transcriptome of human airway epithelium in response to smoking. Sci Rep. 2019;9(1):17600.","journal-title":"Sci Rep"},{"key":"428_CR66","doi-asserted-by":"crossref","unstructured":"Y. Hachim I, Y. Hachim M, Talaat IM, L\u00f3pez-Ozuna VM, Saheb Sharif-Askari N, Halwani R, et al. The molecular basis of gender variations in mortality rates associated with the novel coronavirus (COVID-19) outbreak. https:\/\/www.preprints.org\/manuscript\/202005.0364\/v1 (2020). Accessed 26 Mar 2021.","DOI":"10.20944\/preprints202005.0364.v1"},{"issue":"7","key":"428_CR67","doi-asserted-by":"publisher","first-page":"1871","DOI":"10.1073\/pnas.1511380113","volume":"113","author":"S Ramasamy","year":"2016","unstructured":"Ramasamy S, Saez B, Mukhopadhyay S, Ding D, Ahmed AM, Chen X, et al. Tle1 tumor suppressor negatively regulates inflammation in vivo and modulates NF-\u03baB inflammatory pathway. Proc Natl Acad Sci USA. 2016;113(7):1871\u20136.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"1","key":"428_CR68","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1042\/bj3280199","volume":"328","author":"R Brigelius-Floh\u00e9","year":"1997","unstructured":"Brigelius-Floh\u00e9 R, Friedrichs B, Maurer S, Schultz M, Streicher R. Interleukin-1-induced nuclear factor \u03baB activation is inhibited by overexpression of phospholipid hydroperoxide glutathione peroxidase in a human endothelial cell line. Biochem Journal. 1997;328(1):199\u2013203.","journal-title":"Biochem Journal"},{"issue":"7","key":"428_CR69","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1002\/embj.201387188","volume":"33","author":"JV Chodaparambil","year":"2014","unstructured":"Chodaparambil JV, Pate KT, Hepler MRD, Tsai BP, Muthurajan UM, Luger K, et al. Molecular functions of the TLE tetramerization domain in Wnt target gene repression. EMBO J. 2014;33(7):719\u201331.","journal-title":"EMBO J"},{"issue":"9","key":"428_CR70","doi-asserted-by":"publisher","first-page":"1264","DOI":"10.1093\/hmg\/ddn016","volume":"17","author":"A-A Chassot","year":"2008","unstructured":"Chassot A-A, Ranc F, Gregoire EP, Roepers-Gajadien HL, Taketo MM, Camerino G, et al. Activation of -catenin signaling by Rspo1 controls differentiation of the mammalian ovary. Hum Mol Genet. 2008;17(9):1264\u201377.","journal-title":"Hum Mol Genet"},{"issue":"5","key":"428_CR71","doi-asserted-by":"publisher","first-page":"1102","DOI":"10.1086\/320125","volume":"68","author":"BK Jordan","year":"2001","unstructured":"Jordan BK, Mohammed M, Ching ST, D\u00e9lot E, Chen X-N, Dewing P, et al. Up-regulation of WNT-4 signaling and dosage-sensitive sex reversal in humans. Am J Hum Genet. 2001;68(5):1102\u20139.","journal-title":"Am J Hum Genet"},{"issue":"1","key":"428_CR72","doi-asserted-by":"publisher","first-page":"e0191010","DOI":"10.1371\/journal.pone.0191010","volume":"13","author":"S More","year":"2018","unstructured":"More S, Yang X, Zhu Z, Bamunuarachchi G, Guo Y, Huang C, et al. Regulation of influenza virus replication by Wnt\/\u03b2-catenin signaling. PLoS ONE. 2018;13(1):e0191010.","journal-title":"PLoS ONE"},{"issue":"5","key":"428_CR73","doi-asserted-by":"publisher","first-page":"2001531","DOI":"10.1183\/13993003.01531-2020","volume":"56","author":"EY Choi","year":"2020","unstructured":"Choi EY, Park HH, Kim H, Kim HN, Kim I, Jeon S, et al. Wnt5a and Wnt11 as acute respiratory distress syndrome biomarkers for severe acute respiratory syndrome coronavirus 2 patients. Eur Respir J. 2020;56(5):2001531.","journal-title":"Eur Respir J"},{"issue":"26","key":"428_CR74","doi-asserted-by":"publisher","first-page":"24233","DOI":"10.1074\/jbc.M212389200","volume":"278","author":"Y Takada","year":"2003","unstructured":"Takada Y, Mukhopadhyay A, Kundu GC, Mahabeleshwar GH, Singh S, Aggarwal BB. Hydrogen peroxide activates NF-\u03baB through tyrosine phosphorylation of I\u03baB\u03b1 and serine phosphorylation of p65. J Biol Chem. 2003;278(26):24233\u201341.","journal-title":"J Biol Chem"},{"key":"428_CR75","doi-asserted-by":"publisher","first-page":"290","DOI":"10.3389\/fcimb.2020.00290","volume":"10","author":"L Pruimboom","year":"2020","unstructured":"Pruimboom L. Methylation pathways and SARS-CoV-2 lung infiltration and cell membrane-virus fusion are both subject to epigenetics. Front Cell Infect Microbiol. 2020;10:290.","journal-title":"Front Cell Infect Microbiol"},{"issue":"1","key":"428_CR76","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1186\/s40249-020-00662-x","volume":"9","author":"M-Y Li","year":"2020","unstructured":"Li M-Y, Li L, Zhang Y, Wang X-S. Expression of the SARS-CoV-2 cell receptor gene ACE2 in a wide variety of human tissues. Infect Dis Poverty. 2020;9(1):45.","journal-title":"Infect Dis Poverty"},{"issue":"1","key":"428_CR77","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1186\/s13054-020-02942-2","volume":"24","author":"P Sw\u00e4rd","year":"2020","unstructured":"Sw\u00e4rd P, Edsfeldt A, Reepalu A, Jehpsson L, Rosengren BE, Karlsson MK. Age and sex differences in soluble ACE2 may give insights for COVID-19. Crit Care. 2020;24(1):221.","journal-title":"Crit Care"},{"issue":"16","key":"428_CR78","doi-asserted-by":"publisher","first-page":"9478","DOI":"10.1111\/jcmm.15607","volume":"24","author":"Y Li","year":"2020","unstructured":"Li Y, Xu Q, Ma L, Wu D, Gao J, Chen G, et al. Systematic profiling of ACE2 expression in diverse physiological and pathological conditions for COVID-19\/SARS-CoV-2. J Cell Mol Med. 2020;24(16):9478\u201382.","journal-title":"J Cell Mol Med"},{"issue":"7","key":"428_CR79","doi-asserted-by":"publisher","first-page":"e13168","DOI":"10.1111\/acel.13168","volume":"19","author":"J Chen","year":"2020","unstructured":"Chen J, Jiang Q, Xia X, Liu K, Yu Z, Tao W, et al. Individual variation of the SARS-CoV-2 receptor ACE2 gene expression and regulation. Aging Cell. 2020;19(7):e13168.","journal-title":"Aging Cell"},{"key":"428_CR80","doi-asserted-by":"publisher","unstructured":"Fadason T, Gokuladhas S, Golovina E, Ho D, Farrow S, Nyaga D, et al. A transcription regulatory network within the ACE2 locus may promote a pro-viral environment for SARS-CoV-2 by modulating expression of host factors. http:\/\/biorxiv.org\/lookup\/doi\/https:\/\/doi.org\/10.1101\/2020.04.14.042002 (2020). Accessed 13 Feb 2021.","DOI":"10.1101\/2020.04.14.042002"},{"key":"428_CR81","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1038\/s41467-021-24265-8","volume":"12","author":"E Brady","year":"2021","unstructured":"Brady E, Nielsen MW, Andersen JP, Oertelt-Prigione S. Lack of consideration of sex and gender in clinical trials for COVID-19. Nat Commun. 2021;12:20.","journal-title":"Nat Commun"},{"issue":"6","key":"428_CR82","doi-asserted-by":"publisher","first-page":"1295","DOI":"10.1016\/j.jaci.2020.09.017","volume":"146","author":"C Skevaki","year":"2020","unstructured":"Skevaki C, Karsonova A, Karaulov A, Xie M, Renz H. Asthma-associated risk for COVID-19 development. J Allergy Clin Immun. 2020;146(6):1295\u2013301.","journal-title":"J Allergy Clin Immun"},{"key":"428_CR83","doi-asserted-by":"publisher","first-page":"597753","DOI":"10.3389\/fpubh.2020.597753","volume":"8","author":"R Pansini","year":"2021","unstructured":"Pansini R, Fornacca D. COVID-19 Higher mortality in Chinese regions with chronic exposure to lower air quality. Front Public Health. 2021;8:597753.","journal-title":"Front Public Health"},{"key":"428_CR84","doi-asserted-by":"publisher","unstructured":"Pansini R, Fornacca D. Early evidence of a higher incidence of COVID-19 in the air-polluted regions of eight severely affected countries. http:\/\/medrxiv.org\/lookup\/doi\/https:\/\/doi.org\/10.1101\/2020.04.30.20086496 (2020). Accessed 25 Feb 2021.","DOI":"10.1101\/2020.04.30.20086496"},{"issue":"20","key":"428_CR85","doi-asserted-by":"publisher","first-page":"e90151","DOI":"10.1172\/jci.insight.90151","volume":"1","author":"J Nicodemus-Johnson","year":"2016","unstructured":"Nicodemus-Johnson J, Myers RA, Sakabe NJ, Sobreira DR, Hogarth DK, Naureckas ET, et al. DNA methylation in lung cells is associated with asthma endotypes and genetic risk. JCI Insight. 2016;1(20):e90151.","journal-title":"JCI Insight"},{"key":"428_CR86","doi-asserted-by":"publisher","first-page":"138605","DOI":"10.1016\/j.scitotenv.2020.138605","volume":"726","author":"Y Ogen","year":"2020","unstructured":"Ogen Y. Assessing nitrogen dioxide (NO2) levels as a contributing factor to coronavirus (COVID-19) fatality. Sci Total Environ. 2020;726:138605.","journal-title":"Sci Total Environ"},{"key":"428_CR87","doi-asserted-by":"publisher","first-page":"138704","DOI":"10.1016\/j.scitotenv.2020.138704","volume":"727","author":"Y Zhu","year":"2020","unstructured":"Zhu Y, Xie J, Huang F, Cao L. Association between short-term exposure to air pollution and COVID-19 infection: Evidence from China. Sci Total Environ. 2020;727:138704.","journal-title":"Sci Total Environ"},{"issue":"1","key":"428_CR88","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1080\/22221751.2020.1745095","volume":"9","author":"MJ Loeffelholz","year":"2020","unstructured":"Loeffelholz MJ, Tang Y-W. Laboratory diagnosis of emerging human coronavirus infections \u2013 the state of the art. Emerg Microbes Infect. 2020;9(1):747\u201356.","journal-title":"Emerg Microbes Infect"},{"issue":"7","key":"428_CR89","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1016\/j.jiph.2020.06.005","volume":"13","author":"JP Mathuria","year":"2020","unstructured":"Mathuria JP, Yadav R, Rajkumar B. Laboratory diagnosis of SARS-CoV-2 - A review of current methods. J Infect Public Health. 2020;13(7):901\u20135.","journal-title":"J Infect Public Health"},{"issue":"4","key":"428_CR90","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1289\/EHP595","volume":"125","author":"CV Breton","year":"2017","unstructured":"Breton CV, Marsit CJ, Faustman E, Nadeau K, Goodrich JM, Dolinoy DC, et al. Small-magnitude effect sizes in epigenetic end points are important in children\u2019s environmental health studies: the children\u2019s environmental health and disease prevention research center\u2019s epigenetics working group. Environ Health Perspect. 2017;125(4):511\u201326.","journal-title":"Environ Health Perspect"},{"issue":"16","key":"428_CR91","first-page":"9097","volume":"49","author":"E Gatev","year":"2021","unstructured":"Gatev E, Inkster AM, Negri GL, Konwar C, Lussier AA, Skakkebaek A, et al. Autosomal sex-associated co-methylated regions predict biological sex from DNA methylation. Nucleic Acids Res. 2021;49(16):9097\u2013116.","journal-title":"Nucleic Acids Res"},{"issue":"6509","key":"428_CR92","doi-asserted-by":"publisher","first-page":"3066","DOI":"10.1126\/science.aba3066","volume":"369","author":"M Oliva","year":"2020","unstructured":"Oliva M, Mu\u00f1oz-Aguirre M, Kim-Hellmuth S, Wucher V, Gewirtz AD, Cotter DJ, et al. The impact of sex on gene expression across human tissues. Science. 2020;369(6509):3066.","journal-title":"Science"},{"key":"428_CR93","doi-asserted-by":"crossref","unstructured":"Legato MJ. What determines biological sex? In: The Plasticity of Sex. Elsevier; 2020. p. 1\u201323.","DOI":"10.1016\/B978-0-12-815968-2.00001-3"},{"issue":"5","key":"428_CR94","doi-asserted-by":"publisher","first-page":"385","DOI":"10.7326\/M20-1941","volume":"173","author":"PA Spagnolo","year":"2020","unstructured":"Spagnolo PA, Manson JE, Joffe H. Sex and gender differences in health: what the COVID-19 pandemic can teach us. Ann of Intern Med. 2020;173(5):385\u20136.","journal-title":"Ann of Intern Med"},{"issue":"36","key":"428_CR95","doi-asserted-by":"publisher","first-page":"E1041","DOI":"10.1503\/cmaj.200971","volume":"192","author":"CP Tadiri","year":"2020","unstructured":"Tadiri CP, Gisinger T, Kautzky-Willer A, Kublickiene K, Herrero MT, Raparelli V, et al. The influence of sex and gender domains on COVID-19 cases and mortality. CMAJ. 2020;192(36):E1041\u20135.","journal-title":"CMAJ"},{"key":"428_CR96","doi-asserted-by":"crossref","unstructured":"Lam LL, Emberly E, Fraser HB, Neumann SM, Chen E, Miller GE, et al. Factors underlying variable DNA methylation in a human community cohort. Proc Natl Acad Sci USA. 2012;109(Supplement_2):17253\u201360.","DOI":"10.1073\/pnas.1121249109"},{"key":"428_CR97","doi-asserted-by":"publisher","unstructured":"Ford E, Grimmer MR, Stolzenburg S, Bogdanovic O, Mendoza A de, Farnham PJ, et al. Frequent lack of repressive capacity of promoter DNA methylation identified through genome-wide epigenomic manipulation. http:\/\/biorxiv.org\/lookup\/doi\/https:\/\/doi.org\/10.1101\/170506 (2017). Accessed 26 Feb 2021.","DOI":"10.1101\/170506"},{"issue":"7","key":"428_CR98","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1186\/gb-2013-14-7-126","volume":"14","author":"MJ Jones","year":"2013","unstructured":"Jones MJ, Fejes AP, Kobor MS. DNA methylation, genotype and gene expression: who is driving and who is along for the ride? Genome Biol. 2013;14(7):126.","journal-title":"Genome Biol"}],"container-title":["Epigenetics &amp; Chromatin"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13072-021-00428-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13072-021-00428-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13072-021-00428-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,10]],"date-time":"2023-02-10T16:15:29Z","timestamp":1676045729000},"score":1,"resource":{"primary":{"URL":"https:\/\/epigeneticsandchromatin.biomedcentral.com\/articles\/10.1186\/s13072-021-00428-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,11]]},"references-count":98,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["428"],"URL":"https:\/\/doi.org\/10.1186\/s13072-021-00428-1","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-764250\/v1","asserted-by":"object"}]},"ISSN":["1756-8935"],"issn-type":[{"value":"1756-8935","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,11]]},"assertion":[{"value":"31 July 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 November 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 December 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Largely, data sets were downloaded from two publicly available repositories: Gene Expression Omnibus, GEO, and Genotype-Tissue Expression, GTEx. In addition, research related to the controlled human exposure study presented in this manuscript is in compliance with local, state and national regulations for the ethical treatment of human subjects and ethics approval was obtained from the Research Ethics Board at the University of British Columbia.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"54"}}