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May 3, 20260 citations

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

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WLWulong LiGLGuang LiuDWDan Wei

Key Points

  • This research investigates the genetic similarities between inflammatory bowel disease and ankylosing spondylitis to understand their comorbidities.
  • Utilized genome-wide association study data for inflammatory bowel disease and ankylosing spondylitis.
  • Employed linkage disequilibrium score regression and SUPERGNOVA for genetic signal identification.
  • Applied conditional and conjunctional false discovery rate to quantify genetic overlap.
  • Demonstrated a significant positive genetic correlation between inflammatory bowel disease and ankylosing spondylitis.
  • Identified key shared genetic variants across multiple chromosomal regions.
  • Highlighted enriched pathways that may play a role in the pathogenesis of both diseases.

Abstract

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.

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Cite This Study

Li et al. (2026) studied this question.

synapsesocial.com/papers/69f6e6968071d4f1bdfc74bdhttps://doi.org/10.1038/s41598-026-51117-6
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