{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T12:46:03Z","timestamp":1774529163569,"version":"3.50.1"},"posted":{"date-parts":[[2023,9,1]]},"group-title":"Genetic and Genomic Medicine","reference-count":142,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,5,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Genes on the X-chromosome are extensively expressed in the human brain. However, little is known for the X-chromosome\u2019s impact on the brain anatomy, microstructure, and functional network. We examined 1,045 complex brain imaging traits from 38,529 participants in the UK Biobank. We unveiled potential autosome-X-chromosome interactions, while proposing an atlas outlining dosage compensation (DC) for brain imaging traits. Through extensive association studies, we identified 72 genome-wide significant trait-locus pairs (including 29 new associations) that share genetic architectures with brain-related disorders, notably schizophrenia. Furthermore, we discovered unique sex-specific associations and assessed variations in genetic effects between sexes. Our research offers critical insights into the X-chromosome\u2019s role in the human brain, underscoring its contribution to the differences observed in brain structure and functionality between sexes.<\/jats:p>\n                <jats:sec>\n                  <jats:title>One-sentence Summary<\/jats:title>\n                  <jats:p>We investigated the genetic impact of the X-chromosome and the sex differences in the human brain.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2023.08.30.23294848","type":"posted-content","created":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T16:10:29Z","timestamp":1693584629000},"source":"Crossref","is-referenced-by-count":4,"title":["The pivotal role of the X-chromosome in the genetic architecture of the human brain"],"prefix":"10.64898","author":[{"given":"Zhiwen","family":"Jiang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick F.","family":"Sullivan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tengfei","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bingxin","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xifeng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tianyou","family":"Luo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuai","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter Y.","family":"Guan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason L.","family":"Stein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dajiang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongtu","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024052207500718000_2023.08.30.23294848v2.1","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.tree.2007.03.008","article-title":"The evolution of sex ratios and sex-determining systems","volume":"22","year":"2007","journal-title":"Trends in Ecology & Evolution"},{"key":"2024052207500718000_2023.08.30.23294848v2.2","doi-asserted-by":"publisher","DOI":"10.1038\/190372a0"},{"key":"2024052207500718000_2023.08.30.23294848v2.3","doi-asserted-by":"crossref","first-page":"241","DOI":"10.3389\/fcell.2019.00241","article-title":"Escape From X-Chromosome Inactivation: An Evolutionary Perspective","volume":"7","year":"2019","journal-title":"Front Cell Dev Biol"},{"key":"2024052207500718000_2023.08.30.23294848v2.4","doi-asserted-by":"crossref","first-page":"e348","DOI":"10.1002\/wdev.348","article-title":"Signatures of sex: Sex differences in gene expression in the vertebrate brain","volume":"9","year":"2020","journal-title":"Wiley Interdisciplinary Reviews: Developmental Biology"},{"key":"2024052207500718000_2023.08.30.23294848v2.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0147-3"},{"key":"2024052207500718000_2023.08.30.23294848v2.6","doi-asserted-by":"publisher","DOI":"10.1038\/nature24265"},{"key":"2024052207500718000_2023.08.30.23294848v2.7","doi-asserted-by":"publisher","DOI":"10.1126\/science.aba3066"},{"key":"2024052207500718000_2023.08.30.23294848v2.8","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-018-0148-z"},{"key":"2024052207500718000_2023.08.30.23294848v2.9","unstructured":"S. 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