STAT3-mediated allelic imbalance of novel genetic variant rs1047643 and B cell specific super-enhancer in association with systemic lupus erythematosus

  1. Yanfeng Zhang  Is a corresponding author
  2. Kenneth Day
  3. Devin M Absher  Is a corresponding author
  1. HudsonAlpha Institute for Biotechnology, United States
  2. Zymo Research Corp, United States


Mapping of allelic imbalance (AI) at heterozygous loci has the potential to establish links between genetic risk for disease and biological function. Leveraging multi-omics data for AI analysis and functional annotation, we discovered a novel functional risk variant rs1047643 at 8p23 in association with systemic lupus erythematosus (SLE). This variant displays dynamic AI of chromatin accessibility and allelic expression on FDFT1 gene in B cells with SLE. We further found a B-cell restricted super-enhancer (SE) that physically contacts with this SNP-residing locus, an interaction that also appears specifically in B cells. Quantitative analysis of chromatin accessibility and DNA methylation profiles further demonstrated that the SE exhibits aberrant activity in B cell development with SLE. Functional studies identified that STAT3, a master factor associated with autoimmune diseases, directly regulates both the AI of risk variant and the activity of SE in cultured B cells. Our study reveals that STAT3-mediated SE activity and cis-regulatory effects of SNP rs1047643 at 8p23 locus are associated with B cell deregulation in SLE.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting file; Source Data files have been provided for Figures 2-5.

The following previously published data sets were used

Article and author information

Author details

  1. Yanfeng Zhang

    Genomics, HudsonAlpha Institute for Biotechnology, Huntsville, United States
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3859-3839
  2. Kenneth Day

    Zymo Research Corp, Irvine, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Devin M Absher

    Genomics, HudsonAlpha Institute for Biotechnology, Huntsville, United States
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.


HudsonAlpha Institute for biotechnology funds

  • Yanfeng Zhang
  • Devin M Absher

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Xingyi Guo, Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville 37203, TN, USA., United States

Version history

  1. Received: August 6, 2021
  2. Preprint posted: September 20, 2021 (view preprint)
  3. Accepted: February 18, 2022
  4. Accepted Manuscript published: February 21, 2022 (version 1)
  5. Version of Record published: February 28, 2022 (version 2)


© 2022, Zhang et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.


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  1. Yanfeng Zhang
  2. Kenneth Day
  3. Devin M Absher
STAT3-mediated allelic imbalance of novel genetic variant rs1047643 and B cell specific super-enhancer in association with systemic lupus erythematosus
eLife 11:e72837.

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