An Atlas Characterizing the Shared Genetic Architecture of Inflammatory Bowel Disease with Clinical and Behavioral Traits.

Abstract

Inflammatory bowel disease (IBD) development is a complex, multifactorial process that involves extrinsic and intrinsic factors such as host genetics, the immune system, the gut microbiome, and environmental risks. To help understand the genetic contribution of clinical, behavioral, psychiatric, and diet-related traits, we aim to provide a deep and comprehensive characterization of the shared genetic architecture between IBD and hundreds of potentially related traits. Utilizing publicly available summary statistics from a previously published IBD genome-wide association study and hundreds of traits from the United Kingdom BioBank (UKBB), we performed linkage disequilibrium score regression (LDSR) analysis to estimate cross-trait genetic correlations between Crohn's disease (CD), ulcerative colitis (UC), and IBD summary statistics with the UKBB traits of interest. Nominally significant (P < .05) genetic correlations were observed for 181 traits in overall IBD, 239 traits in CD, and 94 traits in UC. We replicate the known association between smoking behavior and CD/UC, namely that current tobacco smoking has a positive genetic correlation with CD (rg = 0.12, P = 4.2 × 10-4), while "ever smoking" has a negative genetic correlation with UC (rg = -0.07, P = .042). Globally, all 3 strata (IBD, CD, and UC) demonstrated increased genetic correlations for psychiatric-related traits related to anxiety and depression. The present analysis reveals the shared genetic architecture between multiple traits and IBD, CD, and UC. Understanding the relevance of joint occurrences of IBD with psychiatric diseases may moderate management of these diseases for individuals jointly affected by them.