A multilevel study on the genetic relationship between schizophrenia and inflammatory bowel disease

Schizophrenia (SCZ) and Inflammatory Bowel Disease (IBD) represent significant clinical challenges, frequently co-morbid and potentially linked by a genetic correlation. However, the precise mechanism underlying this correlation remains elusive.

we utilized genome-wide association study (GWAS) data for SCZ and IBD to evaluate their genetic correlation. Initially, we performed an overall assessment using Linkage Disequilibrium Score Regression (LDSC), Genetic Covariance Analysis (GNOVA), and High-Dimensional Likelihood (HDL) methods. Subsequently, we conducted a more detailed local analysis using the Local Analysis of Variant Association (LAVA) method. To quantify the genetic overlap between these traits, we employed the Conditional/Joint False Discovery Rate (cond/conjFDR) statistical framework. Finally, by integrating the conjFDR analysis with Multi-Trait GWAS (MTAG), we successfully identified multiple shared genetic loci, shedding light on the genetic intersection between these two traits.

At the genomic level, three independent methods confirmed the overall genetic correlation between SCZ and IBD, including CD and UC. Local genetic correlations were also observed across multiple chromosomal regions. At the single-nucleotide polymorphism (SNP) level, we performed a conjFDR analysis, which indicated a genetic overlap between the two traits. By integrating conjFDR analysis with MTAG, we successfully identified several shared genetic loci, including SLC39A8, BACH2, ZNF365, NOD2, PLCL1, and KIF21B.

The present study provides a novel perspective on the correlation between SCZ and IBD, potentially advancing the understanding of the genetic architecture and mechanisms of co-morbidities in both diseases.