Authors
Samuel J Virolainen, Kathryn Creighton, Maryam Dashtiahangar, Durga Krishnamurthy, Lois Parks, Carmy Forney, Britney Ampadu, Akshata N Rudrapatna, Katelyn A Dunn, Sreeja Parameswaran, Hayley K Hesse, Xiaoting Chen, Andrew VonHandorf, Lee E Edsall, Cailing Yin, Arthur Lynch, Olivia Gittens, Arame A Diouf, Sydney H Jones, Matthew Hass, Ellen Javier, Omer Donmez, Yasine Keddari, Oded Danzinger, Harsha Seelamneni, Bahram Namjou-Khales, Hannah C Ainsworth, Mary E Comeau, Miranda C Marion, Stuart B Glenn, Swapan K Nath, Barry I Freedman, Betty P Tsao, Diane L Kamen, Elizabeth E Brown, Gary S Gilkeson, Graciela S Alarcón, John D Reveille, Judith A James, Lindsey A Criswell, Luis M Vilá, Marta E Alarcón-Riquelme, Michelle Petri, R Hal Scofield, Robert P Kimberly, Rosalind Ramsey-Goldman, Sang-Cheol Bae, Deborah Cunninghame Graham, Timothy J Vyse, Joel M Guthridge, Patrick M Gaffney, Carl D Langefeld, Jennifer A Kelly, Kenneth M Kaufman, Kathy L Sivils, John B Harley, Nan Shen, Lucinda P Lawson, Yuriy Baglaenko, Emily R Miraldi, Brad R Rosenberg, Trevor Siggers, Stephen N Waggoner, Matthew T Weirauch, Leah C Kottyan
Published in
American journal of human genetics. Sep 11, 2026. Epub Sep 11, 2026.
Abstract
Genome-wide association studies have identified genetic polymorphisms at 11p15 associated with systemic lupus erythematosus (lupus). Statistical fine mapping prioritizes a highly prevalent coding haplotype within IRF7. Analysis of ancient DNA confirms that this haplotype has persisted at high frequencies in the global population for millennia. The IRF7 risk haplotype is sufficient to increase nuclear localization of IRF7 and transcriptional activity downstream of pattern recognition receptor pathways. This risk haplotype increases IRF7 DNA-binding strength and alters IRF7 DNA sequence specificity, resulting in genotype-dependent increases in interferon-α production in numerous biological systems, including monocytes and airway epithelial cells. CRISPR engineering of the corresponding risk variant in mouse Irf7 results in both enhanced innate control of virus infection and increased autoantibody titers in a model of autoimmunity. Altogether, we establish a persistent and prominent IRF7 haplotype that amplifies IRF7 activity in a manner that has immunological risks and benefits.
PMID:
42727579
Bibliographic data and abstract were imported from PubMed on 12 Sep 2026.
Read full publication at:
Please sign in
to see all details.
Advertisement
Stats
- Recommendations n/a n/a positive of 0 vote(s)
- Views 9
- Comments 0