TY  - JOUR
A1  - Kukurba, Kimberly R.
A1  - Parsana, Princy
A1  - Balliu, Brunilda
A1  - Smith, Kevin S.
A1  - Zappala, Zachary
A1  - Knowles, David A.
A1  - Favé, Marie-Julie
A1  - Davis, Joe R.
A1  - Li, Xin
A1  - Zhu, Xiaowei
A1  - Potash, James B.
A1  - Weissman, Myrna M.
A1  - Shi, Jianxin
A1  - Kundaje, Anshul
A1  - Levinson, Douglas F.
A1  - Awadalla, Philip
A1  - Mostafavi, Sara
A1  - Battle, Alexis
A1  - Montgomery, Stephen B.
T1  - Impact of the X Chromosome and sex on regulatory variation
Y1  - 2016/06/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 768 
EP  - 777 
DO  - 10.1101/gr.197897.115 
VL  - 26 
IS  - 6 
UR  - http://genome.cshlp.org/content/26/6/768.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. Improving our understanding of these differences offers to elucidate the molecular mechanisms underlying sex-specific traits and diseases. However, to date, most studies have either ignored the X Chromosome or had insufficient power to test for the sex-specific impact of genetic variation. By analyzing whole blood transcriptomes of 922 individuals, we have conducted the first large-scale, genome-wide analysis of the impact of both sex and genetic variation on patterns of gene expression, including comparison between the X Chromosome and autosomes. We identified a depletion of expression quantitative trait loci (eQTL) 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 chromatin accessibility data through ATAC-sequencing to connect sex-specific chromatin accessibility to sex-specific patterns of expression and regulatory variation. As sex-specific regulatory variants discovered in our study can inform sex differences in heritable disease prevalence, we integrated our data with genome-wide association study data for multiple immune traits identifying several traits with significant sex biases in genetic susceptibilities. Together, our study provides genome-wide insight into how genetic variation, the X Chromosome, and sex shape human gene regulation and disease. 
ER  -