Immunosuppression causes dynamic changes in expression QTLs in psoriatic skin

Qian Xiao; Joseph Mears; Aparna Nathan; Kazuyoshi Ishigaki; Yuriy Baglaenko; Noha Lim; Laura A Cooney; Kristina M Harris; Mark S Anderson; David A Fox; Dawn E Smilek; James G Krueger; Soumya Raychaudhuri

doi:10.1038/s41467-023-41984-2

Immunosuppression causes dynamic changes in expression QTLs in psoriatic skin

Nat Commun. 2023 Oct 7;14(1):6268. doi: 10.1038/s41467-023-41984-2.

Authors

Qian Xiao^#^{1

2

3

4}, Joseph Mears^#^{1

2

3

4}, Aparna Nathan^{1

2

3

4

5}, Kazuyoshi Ishigaki^{1

2

3

4

6}, Yuriy Baglaenko^{1

2

3

4}, Noha Lim⁷, Laura A Cooney^{7

8}, Kristina M Harris⁷, Mark S Anderson⁷, David A Fox⁸, Dawn E Smilek⁷, James G Krueger⁹, Soumya Raychaudhuri^{10

11

12

13

14

15}

Affiliations

¹ Center for Data Sciences, Brigham and Women's Hospital, Boston, MA, USA.
² Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
³ Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁴ Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁵ Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
⁶ Laboratory for Human Immunogenetics, RIKEN Center for Integrative Medical Sciences, Yokohama City, Kanagawa, Japan.
⁷ Immune Tolerance Network, Diabetes Center, University of California, San Francisco, San Francisco, CA, USA.
⁸ Division of Rheumatology, Department of Internal Medicine and Clinical Autoimmunity Center of Excellence, University of Michigan, Ann Arbor, MI, USA.
⁹ Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY, USA.
¹⁰ Center for Data Sciences, Brigham and Women's Hospital, Boston, MA, USA. soumya@broadinstitute.org.
¹¹ Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. soumya@broadinstitute.org.
¹² Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. soumya@broadinstitute.org.
¹³ Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA. soumya@broadinstitute.org.
¹⁴ Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA. soumya@broadinstitute.org.
¹⁵ Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, The University of Manchester, Manchester, UK. soumya@broadinstitute.org.

^# Contributed equally.

Abstract

Psoriasis is a chronic, systemic inflammatory condition primarily affecting skin. While the role of the immune compartment (e.g., T cells) is well established, the changes in the skin compartment are more poorly understood. Using longitudinal skin biopsies (n = 375) from the "Psoriasis Treatment with Abatacept and Ustekinumab: A Study of Efficacy"(PAUSE) clinical trial (n = 101), we report 953 expression quantitative trait loci (eQTLs). Of those, 116 eQTLs have effect sizes that were modulated by local skin inflammation (eQTL interactions). By examining these eQTL genes (eGenes), we find that most are expressed in the skin tissue compartment, and a subset overlap with the NRF2 pathway. Indeed, the strongest eQTL interaction signal - rs1491377616-LCE3C - links a psoriasis risk locus with a gene specifically expressed in the epidermis. This eQTL study highlights the potential to use biospecimens from clinical trials to discover in vivo eQTL interactions with therapeutically relevant environmental variables.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Biopsy
Genome-Wide Association Study
Humans
Immunosuppression Therapy
Polymorphism, Single Nucleotide
Psoriasis* / drug therapy
Psoriasis* / genetics
Psoriasis* / pathology
Quantitative Trait Loci* / genetics
Skin / pathology

Abstract

Publication types

MeSH terms

Grants and funding