The shared genetic architecture between acne vulgaris and inflammatory bowel disease: A cross-trait analysis

Acne vulgaris (AV) is clinically associated with inflammatory bowel disease, yet the biological mechanisms driving this association remain unclear. We investigated the shared genetic architecture of AV and inflammatory bowel disease (including ulcerative colitis and Crohn's disease) using data from GWASs. Although AV was genetically weakly correlated with inflammatory bowel disease, MiXeR analyses estimated that 28.2% of the causal variants for inflammatory bowel disease are also causal for AV, with distinct overlap for ulcerative colitis and Crohn's disease. Using the pleiotropic analysis under composite null hypothesis method, we identified 36 shared genomic risk loci, including 27 loci for AV that, to our knowledge, were previously unreported. Downstream functional mapping using MAGMA and S-MultiXcan revealed that these shared variants are predominantly enriched in immune-related tissues (eg, whole blood, spleen) rather than exclusively in the skin or gastrointestinal tracts. Furthermore, pathway analyses consistently highlighted the Jak-signal transducer and activator of transcription signaling cascade as a central shared mechanism. Our findings suggest that the clinical association between AV, ulcerative colitis, and Crohn's disease is driven by shared systemic immune dysregulation. This study provides a refined landscape of pleiotropic genes, prioritizing potentially causal drivers as targets for future mechanistic investigations.