Approved Research

Genetic basis for resistance or susceptibility to diseases conferred by the HLA and KIR loci.

Lay summary

Human leukocyte antigen (HLA) and killer immunoglobulin-like receptors (KIRs) are molecules that interact with one another and regulate our immune system. The sequence of their genes vary extensively across human individuals, leading stronger immune responses in some individuals compared to others.  This in turn leads to differential risks of various diseases, including infectious, autoimmune diseases and cancer, across individuals.

The identification of HLA and KIR gene variation requires special methodology due their high level of variation. Using the genetic data that the UK Biobank can provide, we are able to assign to each patient their HLA and KIR types.  We have established links between certain variants in the KIR and HLA molecules and the differential function of the molecules due to that variation.  These findings allowed us to develop new hypotheses and computational approaches to analyze and understand consequences of HLA and KIR variation.  Specifically, we group individuals based on functional similarities of their HLA and KIR molecules and then analyze these groups in the context of disease.

We would like to apply our knowledge to test the role of KIR and HLA genetic variation in human diseases that are represented in the UK Biobank cohorts.  We believe our findings will improve understanding of inter-individual variation in immune responses and inform development of personalized therapeutic approaches in disease treatment.