Genetic Association in the HLA Region.

ABSTRACT

The MHC/HLA region has been consistently associated with a large number of complex traits, including but not limited to, most immune-mediated ones. Efforts to pinpoint drivers of this commonly encountered association peak at the short arm of chromosome 6, however, have been challenging, owing to the high density of genes and the long and extended linkage disequilibrium that are characteristic of this region.The development of methods to impute classical HLA alleles and amino acids from SNP genotyping data has offered an important additional layer of information to the investigators seeking to fine map the signal in the region. As a result, imputation-aided association analyses are now typically employed to shed light on the relationship of this locus with disease susceptibility and response to drugs.In this chapter we discuss how the signal in the HLA region can be interrogated in practice, from performing the imputation to understanding its output and to incorporating it into downstream analysis. In addition, we recount some of the analytical approaches that are commonly used and suggest ways in which the findings from such imputation-aided analyses can be interpreted.