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• W3198114006 abstract "Background: Natural killer (NK) cells represent a critical component of the innate immune system response against cancer and viral infections, among other diseases. To distinguish healthy host cells from infected or tumor cells, killer immunoglobulin receptors (KIR) on NK cells bind and recognize Human Leukocyte Antigen (HLA) complexes on their target cells. Just like the HLAs they bind, these KIRs exhibit high allelic diversity in the human population. Results: In order to better understand these immunoreceptors, we have developed KIRCLE, a novel method for genotyping individual KIR genes from whole exome sequencing data, and used it to analyze approximately 60,000 patient samples in The Cancer Genome Atlas and UK Biobank. We were able to assess population frequencies for different KIR alleles and demonstrate that, similar to HLA alleles, KIR alleles of different individuals correlate strongly with their ethnicities. In addition, we observed associations between different KIR alleles and HLA alleles, including HLA-B*53 with KIR3DL2*013 (Fisher Exact FDR = 7.64e-51). Finally, we showcased statistically significant associations between KIR alleles and various clinical correlates, including peptic ulcer disease (Fisher Exact FDR = 0.0429) and age of onset of atopy and various KIR alleles (Mann-Whitney-U FDR = 0.0751). Conclusions: KIR polymorphism and NK cells play a critical role in many diseases, often through their interactions with HLA complexes. Peptic ulcer disease and atopy are just two diseases in which NK cells may play a role beyond their classical realm of anti-tumor and anti-viral responses." @default.
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• W3198114006 date "2021-09-04" @default.
• W3198114006 modified "2023-09-27" @default.
• W3198114006 title "KIRCLE: An Analysis of Variations in KIR Genes in The Cancer Genome Atlas and UK Biobank" @default.
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• W3198114006 doi "https://doi.org/10.1101/2021.09.02.458787" @default.
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