Epistatic interactions between killer immunoglobulin-like receptors and human leukocyte antigen ligands are associated with ankylosing spondylitis
Aimee L Hanson, Damjan Vukcevic, Stephen Leslie, Jessica Harris, Kim-Anh Le Cao, Tony J Kenna, Matthew A Brown
PLoS Genetics | PUBLIC LIBRARY SCIENCE | Published : 2020
The killer immunoglobulin-like receptors (KIRs), found predominantly on the surface of natural killer (NK) cells and some T-cells, are a collection of highly polymorphic activating and inhibitory receptors with variable specificity for class I human leukocyte antigen (HLA) ligands. Fifteen KIR genes are inherited in haplotypes of diverse gene content across the human population, and the repertoire of independently inherited KIR and HLA alleles is known to alter risk for immune-mediated and infectious disease by shifting the threshold of lymphocyte activation. We have conducted the largest disease-association study of KIR-HLA epistasis to date, enabled by the imputation of KIR gene and HLA al..View full abstract
Awarded by Australian National Health and Medical Research Council (NHMRC)
Awarded by NHMRC
Awarded by Victorian Life Sciences Computation Initiative
MB is supported by an Australian National Health and Medical Research Council (NHMRC; https://www.nhmrc.gov.au/) Senior Principal Research Fellowship (grant #1024879). AH was supported by an Australian Government Research Training Program Stipend (https://www.education.gov.au/). SL is supported by a NHMRC Career Development Fellowship (grant #1053756) and a Victorian Life Sciences Computation Initiative (https://www.melbournebioinformatics.org.au/; grant #VR0240) funding the Peak Computing Facility at the University of Melbourne. Research at the Murdoch Children's Research Institute was supported by the Victorian Government's Operational Infrastructure Support Program (https://www2.health.vic.gov.au/). K-ALC was supported in part by a NHMRC Career Development Fellowship (grant #1159458). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.