Abstract
Background Genome-wide association studies (GWAS) have discovered thousands of genetic loci associated with various autoimmune diseases and significantly improved our understanding of their pathogenesis. Many loci are associated with multiple autoimmune diseases. However, whether they share the same association mechanisms in these cases has not been well studied.
Methods In this study, we conducted a comprehensive analysis of the association signals for the 15 most common autoimmune diseases using data from the GWAS catalog. In particular, we defined shared and independent association signals based on linkage disequilibrium (LD) among the genetic variants and examined the distinction between locus-sharing and signal-sharing for these diseases. Using genomic resources such as eQTL, histone modification, chromatin accessibility, TF binding, and 3D enhancer-promoter interactions, we annotated these signals and further analyzed the functional implications of these signals.
Results Our analysis identified 353 loci associated with at least two autoimmune diseases (pleiotropic loci) out of a total of 620 loci for all 15 autoimmune diseases. While locus-sharing is common, only 325 signals are shared by multiple autoimmune diseases (pleiotropy), with 1261 signals being disease-specific, suggesting differences in the putative causal genes and/or context-dependent regulation mechanisms. The functional analysis sheds new light on the target genes and association mechanisms, especially on the specific pathways and cell types involved in these diseases.
Conclusions Detailed analyses of shared and specific association signals among the 15 most common autoimmune diseases shed new light on the putative effector genes, relevant cell types, or context-specific regulatory mechanisms for these diseases, and open a window for facilitating further functional characterizations, drug repurposing and discovering novel drug targets.
