Limited Association between Schizophrenia Genetic Risk Factors and Transcriptomic Features
Schizophrenia is a polygenic disorder with many genomic regions contributing to schizophrenia risk. The majority of genetic variants associated with schizophrenia lie in the non-coding genome and are thought to contribute to transcriptional regulation. Extensive transcriptomic dysregulation has been...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-07-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/12/7/1062 |
| _version_ | 1797527095668113408 |
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| author | Alice W. Yu J. David Peery Hyejung Won |
| author_facet | Alice W. Yu J. David Peery Hyejung Won |
| author_sort | Alice W. Yu |
| collection | DOAJ |
| description | Schizophrenia is a polygenic disorder with many genomic regions contributing to schizophrenia risk. The majority of genetic variants associated with schizophrenia lie in the non-coding genome and are thought to contribute to transcriptional regulation. Extensive transcriptomic dysregulation has been detected from postmortem brain samples of schizophrenia-affected individuals. However, the relationship between schizophrenia genetic risk factors and transcriptomic features has yet to be explored. Herein, we examined whether varying gene expression features, including differentially expressed genes (DEGs), co-expression networks, and central hubness of genes, contribute to the heritability of schizophrenia. We leveraged quantitative trait loci and chromatin interaction profiles to identify schizophrenia risk variants assigned to the genes that represent different transcriptomic features. We then performed stratified linkage disequilibrium score regression analysis on these variants to estimate schizophrenia heritability enrichment for different gene expression features. Notably, DEGs and co-expression networks showed nominal heritability enrichment. This nominal association can be partly explained by cellular heterogeneity, as DEGs were associated with the genetic risk of schizophrenia in a cell type-specific manner. Moreover, DEGs were enriched for target genes of schizophrenia-associated transcription factors, suggesting that the transcriptomic signatures of schizophrenia are the result of transcriptional regulatory cascades elicited by genetic risk factors. |
| first_indexed | 2024-03-10T09:38:06Z |
| format | Article |
| id | doaj.art-49051e712b0a4f1494996ca5fd6bbd22 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T09:38:06Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-49051e712b0a4f1494996ca5fd6bbd222023-11-22T03:51:02ZengMDPI AGGenes2073-44252021-07-01127106210.3390/genes12071062Limited Association between Schizophrenia Genetic Risk Factors and Transcriptomic FeaturesAlice W. Yu0J. David Peery1Hyejung Won2Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USADepartment of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USADepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USASchizophrenia is a polygenic disorder with many genomic regions contributing to schizophrenia risk. The majority of genetic variants associated with schizophrenia lie in the non-coding genome and are thought to contribute to transcriptional regulation. Extensive transcriptomic dysregulation has been detected from postmortem brain samples of schizophrenia-affected individuals. However, the relationship between schizophrenia genetic risk factors and transcriptomic features has yet to be explored. Herein, we examined whether varying gene expression features, including differentially expressed genes (DEGs), co-expression networks, and central hubness of genes, contribute to the heritability of schizophrenia. We leveraged quantitative trait loci and chromatin interaction profiles to identify schizophrenia risk variants assigned to the genes that represent different transcriptomic features. We then performed stratified linkage disequilibrium score regression analysis on these variants to estimate schizophrenia heritability enrichment for different gene expression features. Notably, DEGs and co-expression networks showed nominal heritability enrichment. This nominal association can be partly explained by cellular heterogeneity, as DEGs were associated with the genetic risk of schizophrenia in a cell type-specific manner. Moreover, DEGs were enriched for target genes of schizophrenia-associated transcription factors, suggesting that the transcriptomic signatures of schizophrenia are the result of transcriptional regulatory cascades elicited by genetic risk factors.https://www.mdpi.com/2073-4425/12/7/1062schizophreniaGWASLD score regressiondifferentially expressed genesco-expression networkstranscriptional regulation |
| spellingShingle | Alice W. Yu J. David Peery Hyejung Won Limited Association between Schizophrenia Genetic Risk Factors and Transcriptomic Features Genes schizophrenia GWAS LD score regression differentially expressed genes co-expression networks transcriptional regulation |
| title | Limited Association between Schizophrenia Genetic Risk Factors and Transcriptomic Features |
| title_full | Limited Association between Schizophrenia Genetic Risk Factors and Transcriptomic Features |
| title_fullStr | Limited Association between Schizophrenia Genetic Risk Factors and Transcriptomic Features |
| title_full_unstemmed | Limited Association between Schizophrenia Genetic Risk Factors and Transcriptomic Features |
| title_short | Limited Association between Schizophrenia Genetic Risk Factors and Transcriptomic Features |
| title_sort | limited association between schizophrenia genetic risk factors and transcriptomic features |
| topic | schizophrenia GWAS LD score regression differentially expressed genes co-expression networks transcriptional regulation |
| url | https://www.mdpi.com/2073-4425/12/7/1062 |
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