Abstract
SAPHO syndrome is a rare chronic inflammatory disease which is characterized by the comprehensive manifestations of bone, joint, and skin. However, little is known about the pathogenesis of SAPHO syndrome. A genome-wide association study (GWAS) of 49 patients and 121 control subjects have primarily focused on identification of common genetic variants associated with SAPHO, the data were analyzed by classical multiple logistic regression. Later, GWAS findings were further validated using whole exome sequencing (WES) in 16 patients and 15 controls to identify potentially functional pathways involved in SAPHO pathogenesis. In general, 40588 SNPs in genomic regions were associated with P < 0.05 after filter process, only 9 SNPs meet the expected cut-off P-value, however, none of them had association with SAPHO syndrome based on published literatures. And then, 15 pathways were found involved in SAPHO pathogenesis, of them, 6 pathways including osteoclast differentiation, bacterial invasion of epithelial cells, et al., had strong association with skin, osteoarticular manifestations of SAPHO or inflammatory reaction based published research. This study identified aberrant osteoclast differentiation and other pathways were involved in SAPHO syndrome. This finding may give insight into the understanding of pathogenic genes of SAPHO and provide the basis for SAPHO research and treatment.