Abstract
The primary aim of our study was to investigate the genetic correlations, colocalized genes, and causal relationships between craniofacial microsomia (CFM) and 33 diseases (including tumours and respiratory, heart, and kidney diseases). On the basis of extensive summary-level data from genome-wide association studies (GWASs), we evaluated the genetic linkage between CFM and a spectrum of 33 medical conditions using linkage disequilibrium score regression (LDSC). We employed PLACO to identify pleiotropic loci and genes associated with CFM and other diseases. These genes were subsequently subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Finally, the causal effect of CFM on the 33 diseases was assessed through Mendelian randomization (MR). We observed a genetic association between CFM and malignant lymphoma, thyroid cancer, and chronic obstructive pulmonary disease. The PLACO analysis identified 172 potential multi-effect loci (P < 5 × 10- 8). Furthermore, the MAGMA analysis of colocalized single nucleotide polymorphisms (SNPs) revealed that 1,760 SNPs shared genes (P < 0.05/18,345 = 2.726e-6). KEGG analysis revealed enrichment of these genes in the calcium signalling pathway. Finally, Mendelian randomization (MR) analysis suggested that CFM may reduce the risk of developing urolithiasis (IVW: OR = 0.989, 95% CI = 0.979-0.999, p = 0.034). Our study reveals for the first time the genetic associations of CFM with three diseases (malignant lymphoma, thyroid cancer and chronic obstructive pulmonary disease) in an Asian population. In addition, we found a common calcium signalling pathway between these three diseases and CFM. These results provide new insights into the pathogenesis and research potential of CFM.