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Genes can escape this silencing, potentially leading to sex-based differences in disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Across three primary tissue types, we determined XCI status by integrating whole-genome sequencing with bulk RNA-Seq data to assess allele-specific expression (ASE) at heterozygous SNPs. Across all genes and tissues, the average percentage of individuals showing escape was 4.7%. We show that models of full dosage compensation and no dosage compensation are strongly correlated over most parameter space. For G6PD deficiency, we illustrate that in G6PD*B\/G6PD*A- heterozygotes, even if silencing is complete and escape is not associated with disease risk, the allele that is expressed can affect mRNA abundance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>With respect to studies of the genetic architecture of complex traits, our results suggest that a model of full dosage compensation, although not strictly correct for much of chromosome X, is more appropriate than a model of no dosage compensation. We conclude that uncertainty about the model of dosage compensation should not be an impediment to analysis of chromosome X in genetic epidemiology studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12864-025-12352-9","type":"journal-article","created":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T08:56:13Z","timestamp":1763974573000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["X chromosome inactivation across primary human tissues is mostly complete, with significant implications for genetic and clinical studies"],"prefix":"10.1186","volume":"26","author":[{"given":"Daniel","family":"Shriner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayo P.","family":"Doumatey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Lei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mateus H.","family":"Gouveia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karlijn A. 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