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

Summary: Abstract Body: Acne vulgaris (AV) and hidradenitis suppurativa (HS) are associated with inflammatory bowel disease (IBD), suggesting overlapping pathophysiology. However, the exact mechanisms remain to be elucidated. Genome-wide association studies can be used to identify shared genetic variants and link them to biological pathways, providing insight into the overlapping pathophysiology. We analyzed summary statistics of recent European-based genome-wide association studies (GWAS) for AV, HS, and IBD. To explore the overlap in genetic architectures, we calculated genetic correlations and used the MiXeR method to estimate the number of shared causal variants. To identify specific genetic loci that were shared between AV or HS and IBD, we used the pleiotropic analysis under composite null hypothesis (PLACO) method. These genetic loci were used to map candidate genes and biological pathways using FUMA. AV showed a moderate genetic correlation with IBD (rg = 0.16, p = 0.003), particularly with Crohn's disease (rg = 0.16, p = 0.003), but not ulcerative colitis. HS showed a stronger but non-significant genetic correlation with IBD (rg = 0.22, p = 0.21). We found 21 disease-overlapping genetic loci connecting AV to IBD, including 13 novel loci for AV, and 13 loci between HS and IBD, all novel for HS. These loci implicated over 100 unique biological pathways, 16 of which were shared across AV, HS, and IBD. Key pathways included the JAK-STAT signaling pathway and other immune-related pathways. Our findings reveal genetic correlations and overlapping genetic architectures between AV, HS, and IBD, highlighting novel disease-overlapping loci and biological pathways that may inform future therapeutic targets. Willemijn C. Witkam¹, Anna Smak Gregoor¹, Kelsey Van Straalen^{1, 2}, Hieab Adams^{3, 4}, Tamar Nijsten¹, Luba Pardo¹, Sander Lamballais⁵ 1. Dermatology, Erasmus MC, Rotterdam, ZH, Netherlands. 2. Laboratory for Experimental Immunodermatology, Erasmus MC, Rotterdam, ZH, Netherlands. 3. Department of Human Genetics, Radboud universitair medisch centrum, Nijmegen, GE, Netherlands. 4. Latin American Brain Health (BrainLat), Universidad Adolfo Ibanez, Santiago, Santiago Metropolitan Region, Chile. 5. Clinical Genetics, Erasmus MC, Rotterdam, ZH, Netherlands. Clinical Research: Epidemiology and Observational Research