{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T11:48:53Z","timestamp":1759146533987,"version":"3.37.3"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,11,26]],"date-time":"2017-11-26T00:00:00Z","timestamp":1511654400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["145546"],"award-info":[{"award-number":["145546"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genetic Epidemiology"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The expression of X\u2010chromosome undergoes three possible biological processes: X\u2010chromosome inactivation (XCI), escape of the X\u2010chromosome inactivation (XCI\u2010E), and skewed X\u2010chromosome inactivation (XCI\u2010S). Although these expressions are included in various predesigned genetic variation chip platforms, the X\u2010chromosome has generally been excluded from the majority of genome\u2010wide association studies analyses; this is most likely due to the lack of a standardized method in handling X\u2010chromosomal genotype data. To analyze the X\u2010linked genetic association for time\u2010to\u2010event outcomes with the actual process unknown, we propose a unified approach of maximizing the partial likelihood over all of the potential biological processes. The proposed method can be used to infer the true biological process and derive unbiased estimates of the genetic association parameters. A partial likelihood ratio test statistic that has been proved asymptotically chi\u2010square distributed can be used to assess the X\u2010chromosome genetic association. Furthermore, if the X\u2010chromosome expression pertains to the XCI\u2010S process, we can infer the correct skewed direction and magnitude of inactivation, which can elucidate significant findings regarding the genetic mechanism. A population\u2010level model and a more general subject\u2010level model have been developed to model the XCI\u2010S process. Finite sample performance of this novel method is examined via extensive simulation studies. An application is illustrated with implementation of the method on a cancer genetic study with survival outcome.<\/jats:p>","DOI":"10.1002\/gepi.22097","type":"journal-article","created":{"date-parts":[[2017,11,27]],"date-time":"2017-11-27T04:29:05Z","timestamp":1511756945000},"page":"80-94","source":"Crossref","is-referenced-by-count":13,"title":["A unified partial likelihood approach for X\u2010chromosome association on time\u2010to\u2010event outcomes"],"prefix":"10.1002","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0257-8856","authenticated-orcid":false,"given":"Wei","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Biostatistics Princess Margaret Cancer Centre  Toronto ON Canada"},{"name":"Dalla Lana School of Public Health, University of Toronto  Toronto ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meiling","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Princess Margaret Cancer Centre  Toronto ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,11,26]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-1590"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.20637"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.104.031617"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.20051"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03479"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0113596"},{"key":"e_1_2_8_8_1","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/s00439-011-1007-8","article-title":"Chromosome\u2010wide DNA methylation analysis predicts human tissue\u2010specific X inactivation","volume":"130","author":"Cotton A. 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