Genome-annotated bivariate analysis of shared heritability in autoimmune hepatitis with psychiatric comorbidity

Studies indicate a high psychiatric burden in autoimmune hepatitis (AIH) patients, yet research on their genetic links remains unclear. This study comprehensively explores their genetic connections. The correlation metric, genetic correlation (rg), can measure the shared biological basis and explore the genetic architecture. We used the summary statistics from genome-wide association studies (GWAS) to accurately calculate the global and bivariate local genetic correlations between AIH and psychiatric disorders. Cross-trait GWAS meta-analysis for multiple traits can efficiently evaluate single nucleotide polymorphism (SNP) level summary statistics. We employ molecular characteristics to conduct unit tests in various tissues and annotate the corresponding loci. Through multiple genetic covariant tests, we identified 314 unique regions out of 1185 bivariate regions, including chr1p31.1, chr15q25.1, and chr3p14.1. Furthermore, it was discovered that AIH and psychiatric disorders share co-enrichment in multiple brain tissues, including the cerebellum hemisphere, cortex, pituitary, and nucleus accumbens basal ganglia, with PTRHD1, ANKK1, RPS26, YJEFN3, and C2orf69 identified as potential functional genes. The results of the above analyses were verified through multiple colocalization and functional enrichment assessments. Our study has identified pleiotropic genomic regions linking AIH and psychiatric disorders, providing effective strategies for the treatment of diseases.