RESUMEN
BACKGROUND: Inflammatory bowel disease (IBD) and systemic lupus erythematosus (SLE) are autoimmune diseases that often coexist clinically. This phenomenon might be due to shared genetic components. METHODS: Genome-wide association study (GWAS) data for IBD and SLE were analyzed to determine both global and local genetic correlations using three methodologies: linkage disequilibrium score regression (LDSC), genetic covariance analyzer (GNOVA), and SUPERGNOVA. The genetic overlap and risk loci were subsequently examined using the conditional/conjunctional false discovery rate (cond/conjFDR) statistical framework. Furthermore, a multi-trait analysis of MTAG was employed to validate the loci, followed by an LDSC analysis focusing on tissue-specific gene expression. RESULTS: GWAS findings demonstrated a marked global genetic correlation between IBD (including Crohn's disease and ulcerative colitis) and SLE. Locally, SLE showed a strong association with IBD and Crohn's disease on chromosomes 10, 19, and 22. ConjFDR analysis confirmed the genetic overlap and identified relevant genetic risk loci. MTAG further validated several shared susceptibility genes. Additionally, the LDSC-SEG analysis results indicate that IBD (including CD and UC) and SLE are jointly enriched in the tissues of Spleen and Whole Blood. CONCLUSION: This study confirms a genetic overlap between IBD and SLE, identifying marked comorbid genes and offering new insights for treating these diseases.
Asunto(s)
Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Enfermedades Inflamatorias del Intestino , Desequilibrio de Ligamiento , Lupus Eritematoso Sistémico , Lupus Eritematoso Sistémico/genética , Humanos , Enfermedades Inflamatorias del Intestino/genética , Polimorfismo de Nucleótido Simple , Sitios de Carácter CuantitativoRESUMEN
The molecular mechanism regulating petal length in flowers is not well understood. Here we used transient transformation assays to confirm that GhPRGL (proline-rich and GASA-like)-a GASA (gibberellic acid [GA] stimulated in Arabidopsis) family gene-promotes the elongation of ray petals in gerbera (Gerbera hybrida). Yeast one-hybrid screening assay identified a bHLH transcription factor of the jasmonic acid (JA) signaling pathway, here named GhBPE (BIGPETAL), which binds to the GhPRGL promoter and represses its expression, resulting in a phenotype of shortened ray petal length when GhBPE is overexpressed. Further, the joint response to JA and GA of GhBPE and GhPRGL, together with their complementary expression profiles in the early stage of petal growth, suggests a novel GhBPE-GhPRGL module that controls the size of ray petals. GhPRGL promotes ray petal elongation in its early stage especially, while GhBPE inhibits ray petal elongation particularly in the late stage by inhibiting the expression of GhPRGL. JA and GA operate in concert to regulate the expression of GhBPE and GhPRGL genes, providing a regulatory mechanism by which ray petals could grow to a fixed length in gerbera species.