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 (IBD), yet the biological mechanisms driving this association remain unclear. We investigated the shared genetic architecture of AV and IBD (including ulcerative colitis (UC) and Crohn's disease (CD)) by using data from genome-wide association studies. Although AV was genetically weakly correlated with IBD, MiXeR analyses estimated that 28.2% of the causal variants for IBD are also causal for AV, with distinct overlap for UC and CD. Using the pleiotropic analysis under composite null hypothesis (PLACO) method, we identified 36 shared genomic risk loci, including 27 to our knowledge previously unreported loci for AV. Downstream functional mapping using MAGMA and S-MultiXcan revealed that these shared variants are predominantly enriched in immune-related tissues (e.g., whole blood, spleen) rather than exclusively in skin or gastrointestinal tracts. Furthermore, pathway analyses consistently highlighted the JAK-STAT signaling cascade as a central shared mechanism. Our findings suggest that the clinical association between AV, UC, and CD 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 investigation.