TY - JOUR T1 - Impact of the X chromosome and sex on regulatory variation JF - bioRxiv DO - 10.1101/024117 SP - 024117 AU - Kimberly R. Kukurba AU - Princy Parsana AU - Kevin S. Smith AU - Zachary Zappala AU - David A. Knowles AU - Marie-Julie Favé AU - Xin Li AU - Xiaowei Zhu AU - James B. Potash AU - Myrna M. Weissman AU - Jianxin Shi AU - Anshul Kundaje AU - Douglas F. Levinson AU - Philip Awadalla AU - Sara Mostafavi AU - Alexis Battle AU - Stephen B. Montgomery Y1 - 2015/01/01 UR - http://biorxiv.org/content/early/2015/08/07/024117.abstract N2 - 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. ER -