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In placental mammals, an ancient difference between males and females that may make an important contribution to GMV is the different pattern of activation of X chromosomes across cells in females (mosaic inactivation of one the two X chromosomes across cells) vs males (consistent activation of a single X chromosome in all cells). In the current study, variability in hearing thresholds was examined for human listeners with thresholds within the normal range. Initial analyses compared variability in thresholds across males vs. across females. If greater across-male than across-female variability was present, and if these differences in variability related to the different patterns X-chromosome activation in males vs. females, it was expected that correlations between related measures <jats:italic>within<\/jats:italic> a given subject (e.g., hearing thresholds at given frequency in the two ears) would be greater in males than females.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Hearing thresholds at audiometric test frequencies (500\u20136000 or 500\u20138000\u00a0Hz) were extracted from two datasets representing more than 8500 listeners with normal hearing (4590 males, 4376 females). Separate data analyses were carried out on each dataset to compare: (1) relative variability in hearing thresholds across males vs. across females at each test frequency; (2) correlations between both across-ear and within-ear hearing thresholds within\u00a0 males vs. within\u00a0 females, and (3) mean thresholds for females vs. males at each frequency.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>A consistent pattern of GMV in hearing thresholds was seen across frequencies in both datasets. In addition, both across-ear and within-ear correlations between thresholds were consistently greater in males than females. Previous studies have frequently reported lower mean thresholds for females than males for listeners with normal hearing. One of the datasets replicated this result, showing a clear and consistent pattern of lower mean thresholds for females. The second data set did not show clear evidence of this female advantage.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Hearing thresholds showed clear evidence of greater variability across males than across females and higher correlations across related threshold measures within males than within females. The results support a link between the observed GMV and the mosaic pattern of X-activation for females that is not present in males.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13293-022-00457-9","type":"journal-article","created":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T20:04:53Z","timestamp":1663358693000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Sex differences in number of X chromosomes and X-chromosome inactivation in females promote greater variability in hearing among males"],"prefix":"10.1186","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3378-6911","authenticated-orcid":false,"given":"Van","family":"Summers","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,9,16]]},"reference":[{"key":"457_CR1","doi-asserted-by":"publisher","DOI":"10.1037\/12294-000","volume-title":"The descent of man, and selection in relation to sex","author":"C Darwin","year":"1871","unstructured":"Darwin C. 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[] study was reviewed and approved by the Walter Reed National Military Medical Center IRB as an expedited action IAW 32 CFR 219.110 and 32 CFR 219.111 (Criteria for expedited research). The participants provided acknowledgment of consent via a written consent waiver prior to participating in the study. Funding for Grant et al. (2021) was provided by an Applied Research and Technology Development Award through the Defense Medical Research and Development Program (DMRDP), funding opportunity number D13ARATDA_I_13_J8_546. The author received no specific funding for this work.Subjects contributing to the NHANES dataset provided informed consent by signing a Home Interview Consent Form, available at: .Data collection and public availability of the anonymized NHANES data were approved by The National Center for Health Statistics Research Ethics Review Board under protocols #2005-06 and 2011-17.","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 author declares that no competing interests exist.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"49"}}