Impact of the X chromosome and sex on regulatory variation

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

67 Scopus Citations
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Author(s)

  • Kimberly R. Kukurba
  • Princy Parsana
  • Brunilda Balliu
  • Kevin S. Smith
  • Zachary Zappala
  • David A. Knowles
  • Marie-Julie Favé
  • Joe R. Davis
  • Xin Li
  • James B. Potash
  • Myrna M. Weissman
  • Jianxin Shi
  • Anshul Kundaje
  • Douglas F. Levinson
  • Philip Awadalla
  • Sara Mostafavi
  • Alexis Battle
  • Stephen B. Montgomery

Detail(s)

Original languageEnglish
Pages (from-to)768-777
Journal / PublicationGenome Research
Volume26
Issue number6
Publication statusPublished - 1 Jun 2016
Externally publishedYes

Link(s)

Abstract

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.

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Bibliographic Note

Publication details (e.g. title, author(s), publication statuses and dates) are captured on an “AS IS” and “AS AVAILABLE” basis at the time of record harvesting from the data source. Suggestions for further amendments or supplementary information can be sent to lbscholars@cityu.edu.hk.

Citation Format(s)

Impact of the X chromosome and sex on regulatory variation. / Kukurba, Kimberly R.; Parsana, Princy; Balliu, Brunilda et al.
In: Genome Research, Vol. 26, No. 6, 01.06.2016, p. 768-777.

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

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