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
Year: 2021
Type: article
Study design: Observational Study
Abstract: 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.
Source: Frontiers in Immunology
Authors: Richard Ahn, Damjan Vukcevic, Allan Motyer, Joanne Nititham, David McG. Squire, Jill A. Hollenbach, Paul J. Norman, Eva Ellinghaus, Rajan P. Nair, Lam C. Tsoi, Jorge Oksenberg, John Foerster, Wolfgang Lieb, Stephan Weidinger, Andre Franke, James T. Elder, Eric Jorgenson, Stephen Leslie, Wilson Liao
Institutions: University of California, Los Angeles, The University of Melbourne, Murdoch Children's Research Institute, University of California, San Francisco, Christian-Albrechts-Universität zu Kiel, University of Michigan, University of Dundee, University Hospital Schleswig-Holstein, Veterans Health Administration, VA Ann Arbor Healthcare System, Ann Arbor VA Medical Center, Kaiser Permanente
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,950
Funders: Kaiser Permanente, National Institutes of Health, University of California, San Francisco, National Human Genome Research Institute, National Institute of Allergy and Infectious Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Center for Research Resources
Awards: G1839398690, G2401584375, Identification of Psoriatic Arthritis Genes, Linkage Analysis of Familial Psoriasis, Functional Genomics of Psoriasis, G5432599879, G5484367322, G6698405453, Genetic and Genomic Dissection of Psoriatic Arthritis, General Clinical Research Center, G8444803071, G9000035341, G9000249739
OpenAlex ID: W3172187461