Abstract
BACKGROUND: Coeliac disease arises in genetically susceptible individuals, in particular in carriers of HLA-DQ2/DQ8 risk alleles and is associated with various comorbidities. Coeliac disease may confer an increased mortality, but the data are conflicting.
AIMS: We aimed to characterize mortality and morbidity in patients with coeliac disease with a special focus on the role of the number of HLA risk alleles.
METHODS: We studied coeliac disease-associated morbidity and mortality in ~500 000 participants of the UK Biobank including 2482 individuals with the diagnosis of coeliac disease. We used an unbiased, multivariable Phenome-Wide Association Study (PheWAS) method to uncover the coeliac disease-associated disorders. The tag SNP approach was used to divide the coeliac disease subjects into HLA-DQ2/DQ8-based risk categories.
RESULTS: We found 225 ICD-10 codes significantly associated with coeliac disease. During the median follow-up of 10.7 years, coeliac disease individuals (n = 2482) had higher overall mortality (HR 1.6 [95% CI, 1.4-1.8]) than controls and both an increased occurrence of and an increased mortality from cancer, respiratory and cardiovascular diseases (HR 1.4-1.6). Coeliac disease individuals with 2 HLA-DQ2/8 risk alleles had a similar overall mortality as coeliac disease participants with 0-1 HLA-DQ2/8 alleles, but were more likely to die from lymphoproliferative diseases (HR 7.6 [95% CI, 1.01-57.25]).
CONCLUSIONS: Our data suggest that the increased mortality from lymphoproliferative diseases is restricted to those coeliac patients with 2 HLADQ2/8 alleles and that a combination of coeliac disease and HLADQ2/8 alleles is needed to increase the susceptibility. Once confirmed, closer monitoring may be warranted in this high-risk subpopulation.