Genome-wide cross-trait analysis reveals shared genetic architecture between inflammatory bowel disease and ankylosing spondylitis

Patients with inflammatory bowel disease (IBD) and ankylosing spondylitis (AS) are clinically closely related. They suffer from comorbidities, possibly attributed to a shared genetic structure. By utilizing the genome-wide association study (GWAS) data of IBD and AS as the study object, the overall and local genetic associations were first assessed by employing the linkage disequilibrium score regression (LDSC), GNOVA, and high-definition likelihood (HDL). Subsequently, SUPERGNOVA was employed to identify region-specific genetic signals across chromosomes; finally, conditional and conjunctional false discovery rate (cond/conjFDR) and PLACO approaches were applied to quantify genetic overlap and identify shared susceptibility loci between the two disorders. Genome-wide analyses revealed a significant positive genetic correlation between IBD, including its subtypes, and AS. Regional-level analysis further indicated that the two phenotypes share localized genetic architecture across multiple chromosomal segments. ConjFDR assessment confirmed substantial genetic overlap and identified a set of key shared genetic variants and enriched pathways potentially involved in the pathogenesis of both diseases. The present study provides genetic evidence for IBD and AS comorbidity, which may enhance our understanding of the physiopathological aspects of the two diseases.