Improved HLA-based prediction of coeliac disease identifies two novel HLA risk modifiers, DQ6.2 and DQ7.3

Abstract

Abstract Purpose Human Leukocyte Antigen (HLA) testing is useful in the clinical work-up of coeliac disease (CD), with high negative but low positive predictive value. We construct a genomic risk score (GRS) using HLA risk loci to improve CD prediction and guide exclusion criteria. Methods Imputed HLA genotypes for five European CD case-control GWAS (n>15,000) were used to construct and validate an HLA based risk models ( HDQ 15 ). Conditioning on this score, we identified novel HLA interactions which modified CD risk, and integrated these novel alleles into a new risk score ( HDQ 17 ). Results A GRS from HLA risk allele genotypes yields performance equivalent to a state-of-the-art GRS (GRS ..