Phenome of coeliac disease vs. inflammatory bowel disease. 2022

Moritz Kleinjans, and Carolin V Schneider, and Tony Bruns, and Pavel Strnad
Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Germany.

Coeliac disease (CeD) is characterized by gliadin-induced intestinal inflammation appearing in genetically susceptible individuals, such as HLA-DQ2.5 carriers. CeD, as well as other chronic intestinal disorders, such as Crohn's disease (CD) and ulcerative colitis, has been associated with increased morbidity and mortality, but the causes are unknown. We systematically analysed CeD-associated diagnoses and compared them to conditions enriched in subjects with CD/UC as well as in HLA-DQ2.5 carriers without CeD. We compared the overall and cause-specific mortality and morbidity of 3,001 patients with CeD, 2,020 with CD, 4,399 with UC and 492,200 controls in the community-based UK Biobank. Disease-specific phenotypes were assessed with the multivariable Phenome Wide Association Study (PheWAS) method. Associations were adjusted for age, sex and body mass index. All disease groups displayed higher overall mortality than controls (CD: aHR = 1.91[1.70-2.17]; UC: aHR = 1.32 [1.20-1.46]; CeD: aHR = 1.38 [1.22-1.55]). Cardiovascular and cancer-related deaths were responsible for the majority of fatalities. PheWAS analysis revealed 166 Phecodes overrepresented in all three disorders, whereas only ~ 20% of enriched Phecodes were disease specific. Seven of the 58 identified CeD-specific Phecodes were enriched in individuals homozygous for HLA-DQ2.5 without diagnosed CeD. Four out of these seven Phecodes and eight out of 19 HLA-DQ2.5 specific Phecodes were more common in homozygous HLA-DQ2.5 subjects with vs. without CeD, highlighting the interplay between genetics and diagnosis-related factors. Our study illustrates that the morbidity and mortality in CeD share similarities with CD/UC, while the CeD-restricted conditions might be driven by both inherited and acquired factors.

UI MeSH Term Description Entries
D002446 Celiac Disease A malabsorption syndrome that is precipitated by the ingestion of foods containing GLUTEN, such as wheat, rye, and barley. It is characterized by INFLAMMATION of the SMALL INTESTINE, loss of MICROVILLI structure, failed INTESTINAL ABSORPTION, and MALNUTRITION. Gluten Enteropathy,Sprue, Celiac,Sprue, Nontropical,Celiac Sprue,Gluten-Sensitive Enteropathy,Sprue,Disease, Celiac,Enteropathies, Gluten,Enteropathies, Gluten-Sensitive,Enteropathy, Gluten,Enteropathy, Gluten-Sensitive,Gluten Enteropathies,Gluten Sensitive Enteropathy,Gluten-Sensitive Enteropathies,Nontropical Sprue
D003093 Colitis, Ulcerative Inflammation of the COLON that is predominantly confined to the MUCOSA. Its major symptoms include DIARRHEA, rectal BLEEDING, the passage of MUCUS, and ABDOMINAL PAIN. Colitis Gravis,Idiopathic Proctocolitis,Inflammatory Bowel Disease, Ulcerative Colitis Type,Ulcerative Colitis
D003424 Crohn Disease A chronic transmural inflammation that may involve any part of the DIGESTIVE TRACT from MOUTH to ANUS, mostly found in the ILEUM, the CECUM, and the COLON. In Crohn disease, the inflammation, extending through the intestinal wall from the MUCOSA to the serosa, is characteristically asymmetric and segmental. Epithelioid GRANULOMAS may be seen in some patients. Colitis, Granulomatous,Enteritis, Granulomatous,Enteritis, Regional,Ileitis, Regional,Ileitis, Terminal,Ileocolitis,Crohn's Disease,Crohn's Enteritis,Inflammatory Bowel Disease 1,Regional Enteritis,Crohns Disease,Granulomatous Colitis,Granulomatous Enteritis,Regional Ileitides,Regional Ileitis,Terminal Ileitis
D005903 Gliadin Simple protein, one of the prolamines, derived from the gluten of wheat, rye, etc. May be separated into 4 discrete electrophoretic fractions. It is the toxic factor associated with CELIAC DISEASE. alpha-Gliadin,alpha Gliadin
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D015212 Inflammatory Bowel Diseases Chronic, non-specific inflammation of the GASTROINTESTINAL TRACT. Etiology may be genetic or environmental. This term includes CROHN DISEASE and ULCERATIVE COLITIS. Bowel Diseases, Inflammatory,Inflammatory Bowel Disease

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