4.7 Article

Phenome-wide association study in adult coeliac disease: role of HLA subtype

Journal

ALIMENTARY PHARMACOLOGY & THERAPEUTICS
Volume 53, Issue 4, Pages 510-518

Publisher

WILEY
DOI: 10.1111/apt.16206

Keywords

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Funding

  1. Deutsche Forschungsgemeinschaft [SFB 1382 (ID 403224013), STR 1095/6-1]

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Patients with coeliac disease have higher overall mortality compared to controls, and they are more prone to developing and dying from cancer, respiratory, and cardiovascular diseases. Those with 2 HLA-DQ2/DQ8 risk alleles are more likely to die from lymphoproliferative diseases.
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 similar to 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.

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