| The genome-wide association study has identified many pleiotropic loci associated with complex phenotypes.However,the genetic mechanisms of most complex phenotypes have not been systematically explained so far.By using the optimized cFDR statistical method,deep data mining can be performed on a large number of GWAS data in the past to find new associated genetic loci of complex diseases and effectively reveal the potential roles and relevance level of these sites.It provides guidance for the shared etiology of the two diseases and offers theoretical basis for the study of disease mechanisms.ObjectiveThis study intends to use optimized cFDR statistical methods for in-depth excavation of related GWAS data to explore the associated genetic loci of chronic kidney disease CKD and OP.MethodsIn this paper,two relevant GWAS data of CKD and OP diseases in 2015 were analyzed using the cFDR method with optimized algorithm,and the SNPs not related to the main phenotype in the SNPs with P values below the threshold were calculated.Conditional Q-Q plots were used to assess the degree of enrichment for the associated genetic variation of CKD and OP.The cFDR<0.05 was used as the criterion to determine the genetic variation of the two related traits;combined cFDR<0.05 was used to determine the common pleiotropic sites of CKD and OP ยท demonstrated with Manhattan plots.Results1.Conditions Q-Q plots show that CKD and OP both have higher multi-effect enrichment;2.Combining the 2 traits of CKD and the 3 traits of OP by the statistical method of cFDR.This study identified 97 mutations that were associated with CKD,of which 42 were newly discovered loci associated with 20 chromosomes and were registered on 36 genes;and there are 134 mutations that were associated with OP,of which 55 were newly discovered loci associated with 16 chromosomes and were registered on 48 genes.3.Through the conjuction cFDR statistical methods,we identified 4 new common pleiotropic sites of CKD and OP,respectively rs7150435,rs4886755,rs7176579,rs7586601.Combining the speculative studies on the function of related genes in common multiple-effect sites,three sites of rs7150435,rs4886755,and rs7586601 indicate that CKD and OP may have etiological or genetic mechanisms.Conclusions1.In this study,four new pleiotropic sites and 231 related mutation sites associated with CKD and OP were successfully identified using the cFDR and ccFDR methods.2.This study confirmed the existence of gene polymorphism between CKD and OP.The hundreds of loci obtained confirmed the significant correlation between CKD and OP,suggesting that there may be some kind of causal association between the two diseases.3.The cFDR method has high feasibility in the identification of disease-related genes and exploration of common pathogenic genes,providing a new path for identification of pathogenic gene loci. |
