Journal article

Improved HLA-based prediction of coeliac disease identifies two novel genetic interactions

Michael Erlichster, Justin Bedo, Efstratios Skafidas, Patrick Kwan, Adam Kowalczyk, Benjamin Goudey

European Journal of Human Genetics | Springer Nature | Published : 2020


Human Leucocyte 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 genotypes to improve CD prediction and guide exclusion criteria. Imputed HLA genotypes for five European CD case-control GWAS (n > 15,000) were used to construct and validate an interpretable HLA-based risk model (HDQ15), which shows statistically significant improvements in predictive performance upon all previous HLA-based risk models. Conditioning on this model, we find two novel associations, HLA-DQ6.2 and HLA-DQ7.3, that interact significantly with HLA-DQ2.5 (p = 2.51 × 10−9, 1.99 × 10..

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