| Title: | Phenome-wide association study in adult coeliac disease: role of HLA subtype |
| Journal: | Alimentary Pharmacology & Therapeutics |
| Published: | 5 Dec 2020 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/33280147/ |
| DOI: | https://doi.org/10.1111/apt.16206 |
| URL: | https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/apt.16206 |
| Citations: | 10 (3 in last 2 years) as of 8 Aug 2024 |
Publication 12890
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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.</p>
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.</p>
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.</p>
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]).</p>
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.</p>
6 Keywords
- Adult
- Alleles
- Celiac Disease
- Genetic Predisposition to Disease
- Humans
- Risk Factors
5 Authors
- Carolin V. Schneider
- Moritz Kleinjans
- Malin Fromme
- Kai Markus Schneider
- Pavel Strnad
1 Application
| Application ID | Title |
|---|---|
| 47527 | Analysis of Alpha1-Antitrypsin related comorbidities |
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