Journal Article

Comorbidity Between Inflammatory Bowel Disease and Asthma and Allergic Diseases: A Genetically Informed Study

Smew, Awad I, Brew, Bronwyn K, Gong, Tong, Ludvigsson, Jonas F, Lu, Yi, Harder, Arvid, Almqvist, Catarina, Lundholm, Cecilia, Kuja-Halkola, Ralf

2024

Overview

Abstract Background Little is known about shared origins between inflammatory bowel disease (IBD) and allergic diseases (asthma, allergic rhinitis, and eczema). We aimed to expand current knowledge on the etiological sources of comorbidities between these disorders using a range of genetically informed methods. Methods Within-individual and familial co-aggregation analysis was applied to 2 873 445 individuals born in Sweden from 1987 to 2014 and their first- and second-degree relatives. Quantitative genetic modeling was applied to 38 723 twin pairs to decompose the genetic and environmental sources for comorbidity. Polygenic risk score analysis between IBD and allergic diseases was conducted in 48 186 genotyped twins, and linkage disequilibrium score regression was applied using publicly available data to explore the genetic overlap. Results IBD was associated with asthma (adjusted odds ratio [aOR], 1.35; 95% confidence interval [CI], 1.30 to 1.40), allergic rhinitis (aOR, 1.27; 95% CI, 1.20 to 1.34), and eczema (aOR, 1.47; 95% CI, 1.38 to 1.56), with similar estimates for ulcerative colitis or Crohn’s disease. The ORs for familial co-aggregation decreased with decreasing genetic relatedness. Quantitative genetic modeling revealed little evidence of common genetic factors between IBD and allergic diseases (eg, IBD and allergic rhinitis; genetic correlation ra = 0.06; 95% CI, −0.03 to 0.15) but did reveal some evidence of unique environmental factors between IBD and eczema (re = 0.16; 95% CI, 0.00 to 0.32). Molecular genetic analyses were similarly null for IBD and allergic diseases, except for a slight association between Crohn’s disease polygenic risk score and eczema (OR, 1.09; 95% CI, 1.06 to 1.12). Conclusions We found little evidence to support a shared origin between IBD and any allergic disease but weak evidence for shared genetic and unique environmental components for IBD and eczema. Lay Summary Comorbidities between inflammatory bowel disease (IBD) with asthma and allergic diseases have been documented, but shared origin remains unknown. Using multiple genetically informed approaches, we found little evidence of a shared origin explaining the comorbidities of IBD with asthma and allergic rhinitis but weak evidence for IBD and eczema.

• Publisher: Oxford University Press
• Subject: Adolescent / Adult / Asthma / Asthma - epidemiology / Asthma - genetics / Child / Comorbidity / Crohn's disease / Eczema / Eczema - epidemiology / Eczema - genetics / Female / Genetic Predisposition to Disease / Hay fever / Humans / Hypersensitivity - epidemiology / Hypersensitivity - genetics / Inflammatory bowel disease / Inflammatory Bowel Diseases - epidemiology / Inflammatory Bowel Diseases - genetics / Male / Middle Aged / Quantitative genetics / Rhinitis / Rhinitis, Allergic - epidemiology / Rhinitis, Allergic - genetics / Risk Factors / Sweden - epidemiology / Translational Research / Young Adult