Genetic variants shape single-cell chromatin accessibility and disease risk
T cells. A graph neural network trained on both eQTL and caQTL layers inferred peak-gene links in unpaired multiome data with up to 17.2% higher accuracy than QTL-agnostic data, uncovering 128 additional transcription factor-target pairs (22% increase). Together, these results show that genetic variants shape chromatin accessibility in a cell-type-specific and cell-state-specific manner, influencing immune function and disease risk.
Authors
- Albert Henry (ORCID: https://orcid.org/0000-0001-7422-2288)
- Daniel G. MacArthur (ORCID: https://orcid.org/0000-0002-5771-2290)
- Kyle Kai‐How Farh (ORCID: https://orcid.org/0000-0001-6947-8537)
- Katrina M. de Lange
- Angli Xue (ORCID: https://orcid.org/0000-0002-0285-0426)
- Rachael A. McCloy (ORCID: https://orcid.org/0000-0001-7791-4044)
- Eyal David (ORCID: https://orcid.org/0000-0002-9020-2364)
- Venessa T. Chin (ORCID: https://orcid.org/0000-0002-4630-4451)
- Alex William Hewitt (ORCID: https://orcid.org/0000-0002-5123-5999)
- Hope A. Tanudisastro (ORCID: https://orcid.org/0000-0002-4561-305X)
- Joseph E. Powell (ORCID: https://orcid.org/0000-0002-5070-4124)
- Hao Lawrence Huang (ORCID: https://orcid.org/0000-0001-8960-8941)
- Alkes L. Price (ORCID: https://orcid.org/0000-0002-2971-7975)
- Anne Senabouth (ORCID: https://orcid.org/0000-0002-8798-9821)
- Anna S. E. Cuomo (ORCID: https://orcid.org/0000-0001-5168-6979)
- Arthur S. Lee (ORCID: https://orcid.org/0000-0002-4513-4630)
- Drew R. Neavin (ORCID: https://orcid.org/0000-0002-1783-6491)
- Peter C. Allen (ORCID: https://orcid.org/0000-0002-3950-9539)
- Elizabeth Dorans (ORCID: https://orcid.org/0000-0002-8360-9764)
- Ling Chen (ORCID: https://orcid.org/0009-0005-1326-4069)
- Wei Zhou (ORCID: https://orcid.org/0000-0001-7719-0859)
- Caitlin Bartie
- Eleanor Spenceley (ORCID: https://orcid.org/0009-0000-5543-2810)
- Eszter Sagi-Zsigmond (ORCID: https://orcid.org/0000-0002-7703-2153)
- Oscar A Dong (ORCID: https://orcid.org/0009-0009-8275-2989)
- Yijia Christiana Liu (ORCID: https://orcid.org/0009-0001-2078-651X)
- Gemma A. Figtree
- Blake Bowen
- Jianan Fan
- Zhen Qiao
- Linfeng Hu
Institutions
- Broad Institute (US)
- The University of Sydney (AU)
- University of Tasmania (AU)
- University of Helsinki (FI)
- Harvard University (US)
- Garvan Institute of Medical Research (AU)
- Illumina (United States) (US)
- Royal North Shore Hospital (AU)
- Royal Hobart Hospital (AU)
- UNSW Sydney (AU)
- St Vincent's Hospital Sydney (AU)
- Massachusetts General Hospital (US)
- Institute for Molecular Medicine Finland (FI)
- Murdoch Children's Research Institute (AU)
- The Kinghorn Cancer Centre (AU)
- Stanley Center for Psychiatric Research (US)
- Menzies Institute for Medical Research (AU)
Publication Details
- Journal
- Nature
- Published
- 2026-10-28
- DOI
- https://doi.org/10.1038/s41586-026-11173-4
- Citations
- 3
- Primary Topic
- Genomics and Chromatin Dynamics
- Type
- article
- Field-Weighted Citation Impact
- 6.20