Frontiers in Immunology (Jun 2021)
Large-Scale Imputation of KIR Copy Number and HLA Alleles in North American and European Psoriasis Case-Control Cohorts Reveals Association of Inhibitory KIR2DL2 With Psoriasis
- Richard Ahn,
- Richard Ahn,
- Damjan Vukcevic,
- Damjan Vukcevic,
- Damjan Vukcevic,
- Allan Motyer,
- Allan Motyer,
- Joanne Nititham,
- David McG. Squire,
- David McG. Squire,
- Jill A. Hollenbach,
- Paul J. Norman,
- Eva Ellinghaus,
- Rajan P. Nair,
- Lam C. Tsoi,
- Lam C. Tsoi,
- Lam C. Tsoi,
- Jorge Oksenberg,
- John Foerster,
- Wolfgang Lieb,
- Stephan Weidinger,
- Andre Franke,
- James T. Elder,
- James T. Elder,
- Eric Jorgenson,
- Stephen Leslie,
- Stephen Leslie,
- Stephen Leslie,
- Wilson Liao
Affiliations
- Richard Ahn
- Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, United States
- Richard Ahn
- Institute for Quantitative and Computational Biosciences, University of California, Los Angeles, Los Angeles, CA, United States
- Damjan Vukcevic
- Melbourne Integrative Genomics, The University of Melbourne, Parkville, VIC, Australia
- Damjan Vukcevic
- School of Mathematics and Statistics, The University of Melbourne, Parkville, VIC, Australia
- Damjan Vukcevic
- Clinical Epidemiology and Biostatistics Unit, Murdoch Children’s Research Institute, Parkville, VIC, Australia
- Allan Motyer
- Melbourne Integrative Genomics, The University of Melbourne, Parkville, VIC, Australia
- Allan Motyer
- School of Mathematics and Statistics, The University of Melbourne, Parkville, VIC, Australia
- Joanne Nititham
- Department of Dermatology, University of California, San Francisco, San Francisco, CA, United States
- David McG. Squire
- Melbourne Integrative Genomics, The University of Melbourne, Parkville, VIC, Australia
- David McG. Squire
- School of Mathematics and Statistics, The University of Melbourne, Parkville, VIC, Australia
- Jill A. Hollenbach
- Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, United States
- Paul J. Norman
- Division of Personalized Medicine, Department of Immunology and Microbiology, University of Colorado, San Francisco, CA, United States
- Eva Ellinghaus
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany
- Rajan P. Nair
- 0Department of Dermatology, University of Michigan, Ann Arbor, MI, United States
- Lam C. Tsoi
- 0Department of Dermatology, University of Michigan, Ann Arbor, MI, United States
- Lam C. Tsoi
- 1Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, United States
- Lam C. Tsoi
- 2Department of Computational Medicine & Bioinformatics, University of Michigan, Ann Arbor, MI, United States
- Jorge Oksenberg
- Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, United States
- John Foerster
- 3College of Medicine, Dentistry, and Nursing, University of Dundee, Dundee, United Kingdom
- Wolfgang Lieb
- 4Institute of Epidemiology, Christian-Albrechts-University of Kiel, Kiel, Germany
- Stephan Weidinger
- 5Department of Dermatology, University Hospital Schleswig Holstein, Kiel, Germany
- Andre Franke
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany
- James T. Elder
- 0Department of Dermatology, University of Michigan, Ann Arbor, MI, United States
- James T. Elder
- 6Ann Arbor Veterans Affairs Hospital, Dermatology, Ann Arbor, MI, United States
- Eric Jorgenson
- 7Division of Research, Kaiser Permanente, Oakland, CA, United States
- Stephen Leslie
- Melbourne Integrative Genomics, The University of Melbourne, Parkville, VIC, Australia
- Stephen Leslie
- School of Mathematics and Statistics, The University of Melbourne, Parkville, VIC, Australia
- Stephen Leslie
- 8School of Biosciences, The University of Melbourne, Parkville, VIC, Australia
- Wilson Liao
- Department of Dermatology, University of California, San Francisco, San Francisco, CA, United States
- DOI
- https://doi.org/10.3389/fimmu.2021.684326
- Journal volume & issue
-
Vol. 12
Abstract
Killer cell immunoglobulin-like receptors (KIR) regulate immune responses in NK and CD8+ T cells via interaction with HLA ligands. KIR genes, including KIR2DS1, KIR3DL1, and KIR3DS1 have previously been implicated in psoriasis susceptibility. However, these previous studies were constrained to small sample sizes, in part due to the time and expense required for direct genotyping of KIR genes. Here, we implemented KIR*IMP to impute KIR copy number from single-nucleotide polymorphisms (SNPs) on chromosome 19 in the discovery cohort (n=11,912) from the PAGE consortium, University of California San Francisco, and the University of Dundee, and in a replication cohort (n=66,357) from Kaiser Permanente Northern California. Stratified multivariate logistic regression that accounted for patient ancestry and high-risk HLA alleles revealed that KIR2DL2 copy number was significantly associated with psoriasis in the discovery cohort (p ≤ 0.05). The KIR2DL2 copy number association was replicated in the Kaiser Permanente replication cohort. This is the first reported association of KIR2DL2 copy number with psoriasis and highlights the importance of KIR genetics in the pathogenesis of psoriasis.
Keywords
