%0 Journal Article %A Kimberly R. Kukurba %A Princy Parsana %A Kevin S. Smith %A Zachary Zappala %A David A. Knowles %A Marie-Julie Favé %A Xin Li %A Xiaowei Zhu %A James B. Potash %A Myrna M. Weissman %A Jianxin Shi %A Anshul Kundaje %A Douglas F. Levinson %A Philip Awadalla %A Sara Mostafavi %A Alexis Battle %A Stephen B. Montgomery %T Impact of the X chromosome and sex on regulatory variation %D 2015 %R 10.1101/024117 %J bioRxiv %P 024117 %X The X chromosome, with its unique mode of inheritance, contributes to differences between the sexes at a molecular level, including sex-specific gene expression and sex-specific impact of genetic variation. We have conducted an analysis of the impact of both sex and the X chromosome on patterns of gene expression identified through transcriptome sequencing of whole blood from 922 individuals. We identified that genes on the X chromosome are more likely to have sex-specific expression compared to the autosomal genes. Furthermore, we identified a depletion of regulatory variants on the X chromosome, especially among genes under high selective constraint. In contrast, we discovered an enrichment of sex-specific regulatory variants on the X chromosome. To resolve the molecular mechanisms underlying such effects, we generated and connected sex-specific chromatin accessibility to sex-specific expression and regulatory variation. As sex-specific regulatory variants can inform sex differences in genetic disease prevalence, we have integrated our data with genome-wide association study data for multiple immune traits and to identify traits with significant sex biases. Together, our study provides genome-wide insight into how the X chromosome and sex shape human gene regulation and disease. %U https://www.biorxiv.org/content/biorxiv/early/2015/08/07/024117.full.pdf