Limited Association between Schizophrenia Genetic Risk Factors and Transcriptomic Features

被引:4
|
作者
Yu, Alice W. [1 ]
Peery, J. David [2 ,3 ]
Won, Hyejung [4 ,5 ]
机构
[1] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA
[2] Univ N Carolina, Dept Comp Sci, Chapel Hill, NC 27599 USA
[3] Univ N Carolina, Dept Stat & Operat Res, Chapel Hill, NC 27599 USA
[4] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA
[5] Univ N Carolina, Neurosci Ctr, Chapel Hill, NC 27599 USA
关键词
schizophrenia; GWAS; LD score regression; differentially expressed genes; co-expression networks; transcriptional regulation; GENOME-WIDE ASSOCIATION; EXPRESSION; DYSFUNCTION;
D O I
10.3390/genes12071062
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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.
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页数:13
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