The Genetic Overlap Between Schizophrenia And Cardiometabolic Diseases

Objective: Exploring candidate genes and pathways for schizophrenia and cardiometabolic diseases(CMD),and identifying candidate genes and pathways shared between these two classes of diseases.Methods: The genome-wide association studies(GWAS)summary statistics of schizophrenia and CMD,and the expression quantitative trait loci(eQTL)datasets of each tissue included in this study were obtained from publicly available databases.Firstly,we used positional mapping of FUMA to functionally annotate of traits-associated genetic variants from GWAS summary statistics of schizophrenia and CMD.We then performed the analysis methods of FUMA,Sherlock,SMR,UTMOST,FOCUS and DEPICT,which integrated the GWAS summary statistics of schizophrenia and CMD,and tissue-specific expression quantitative trait loci(eQTL)data to predicate the candidate genes for schizophrenia and CMD.Finally,we performed gene-set enrichment analysis with GWAS summary statistics using the software of GSA-SNP2 and MAGMA to identify the potential biological pathways for schizophrenia and CMD.Results: By integrating the results from different approaches including FUMA,Sherlock,SMR,UTMOST,FOCUS and DEPICT,we revealed 21 potential candidate genes shared between schizophrenia and CMD.Specifically,VRK2,NT5C2,INO80 E,YPEL3 and MAPK3 are the common candidate genes of schizophrenia and obesity;NT5C2,FES and FURIN are the candidate genes for both schizophrenia and coronary artery disease;ARL6IP4,OGFOD2,PITPNM2,CDK2AP1,C12orf65,ABCB9,SETD8,MPHOSPH9,SREBF1,TOM1L2 and GATAD2 A are associated with the comorbidity of schizophrenia and type 2 diabetes;SLC39A8,AMBRA1,C12orf65 and SETD8 are associated with the comorbidity of schizophrenia and high-density lipoproteins;GATAD2A and TM6SF2 are the common candidate genes of schizophrenia,triglycerides and total cholesterol.In addition,we also found that MAPK-TRK signaling pathway is related to schizophrenia and obesity,and growth hormone signaling,and regulation of insulin secretion signaling are the common biological pathways shared between schizophrenia and type 2 diabetes.Conclusion: We revealed 21 potential candidate genes that are likely to be shared between schizophrenia and CMD.These genes include VRK2,SLC39A8,NT5C2,AMBRA1,ARL6IP4,OGFOD2,PITPNM2,CDK2AP1,C12orf65,ABCB9,SETD8,MPHOSPH9,FES,FURIN,INO80 E,YPEL3,MAPK3,SREBF1,TOM1L2,GATAD2 A and TM6SF2.In addition,we also identified three biological pathways(MAPK-TRK signaling,growth hormone signaling,and regulation of insulin secretion signaling)are the common biological pathways shared between schizophrenia and CMD.