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.

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
Year of publication:
2021
Volume:
12
Issue:
-
Issn:
1664-3224
Journal title abbreviated:
Front Immunol
Journal title long:
Frontiers in immunology
Impact factor:
5.085
Abstract:
Killer cell immunoglobulin-like receptors (KIR) regulate immune responses in NK and CD8+ T cells <i>via</i> 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.