Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Genome-wide association studies (GWAS) have identified abundant risk loci associated with schizophrenia (SCZ), cardiometabolic disease (CMD) including body mass index, coronary artery diseases, type 2 diabetes, low- and high-density lipoprotein, total cholesterol, and triglycerides. Although recent studies have suggested that genetic risk shared between these disorders, the pleiotropic genes and biological pathways shared between them are still vague. Here we integrated comprehensive multi-dimensional data from GWAS, expression quantitative trait loci (eQTL), and gene set database to systematically identify potential pleiotropic genes and biological pathways shared between SCZ and CMD. By integrating the results from different approaches including FUMA, Sherlock, SMR, UTMOST, FOCUS, and DEPICT, we revealed 21 pleiotropic genes that are likely to be shared between SCZ and CMD. These genes include VRK2, SLC39A8, NT5C2, AMBRA1, ARL6IP4, OGFOD2, PITPNM2, CDK2AP1, C12orf65, ABCB9, SETD8, MPHOSPH9, FES, FURIN, INO80E, YPEL3, MAPK3, SREBF1, TOM1L2, GATAD2A, and TM6SF2. In addition, we also performed the gene-set enrichment analysis using the software of GSA-SNP2 and MAGMA with GWAS summary statistics and identified three biological pathways (MAPK-TRK signaling, growth hormone signaling, and regulation of insulin secretion signaling) shared between them. Our study provides insights into the pleiotropic genes and biological pathways underlying mechanisms for the comorbidity of SCZ and CMD. However, further genetic and functional studies are required to validate the role of these potential pleiotropic genes and pathways in the etiology of the comorbidity of SCZ and CMD, which should provide potential targets for future diagnostics and therapeutics.
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PMID:Integrated Analysis of Summary Statistics to Identify Pleiotropic Genes and Pathways for the Comorbidity of Schizophrenia and Cardiometabolic Disease. 3242 17

Recent genome-wide association studies (GWAS) have identified multiple schizophrenia-associated risk loci. However, the potential functional (or causal) variant remains largely unknown for each of the identified risk locus. In this study, we utilized different functional annotation approaches (i.e., CADD, Eigen, GWAVA, RegulomeDB and LINSIGHT) to prioritize the most possible functional variant at schizophrenia risk locus 12q24.31, a risk locus that showed genome-wide significant association with schizophrenia. We found that four functional annotation methods prioritized rs7304782 as a potential functional variant at 12q24.31, suggesting the potential functional consequence of rs7304782. Consistent with the functional annotation, reporter gene assays showed that different allele of rs7304782 affected the luciferase activity significantly, further supporting that rs7304782 is a functional variant. We further performed genetic association study and validated that rs7304782 is also associated with schizophrenia in Chinese population (N=4,291 cases and 7,847 controls), with the same risk allele as in European population. Expression quantitative trait loci (eQTL) analysis indicated that rs7304782 was significantly associated with the expression of OGFOD2 in human brain tissues. Of note, differential expression analysis indicated that OGFOD2 was significantly down-regulated in schizophrenia cases compared with controls. Our study identified a potential functional variant (i.e., rs7304782) at schizophrenia risk locus 12q24.31 and suggested that this functional variant may confer schizophrenia risk through regulating OGFOD2 expression.
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PMID:Identification of a functional SNP rs7304782 at schizophrenia risk locus 12q24.31 and validation of its association with schiz ophrenia in Chinese populations. 3307 Jan 9