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• W3044338046 abstract "Abstract Bipolar disorder (BD) is a highly heritable neuropsychiatric disorder characterized by recurrent episodes of depression and mania. Since the signals identified by genome-wide association study (GWAS) often reside in the non-coding regions, understanding the biological relevance of these genetic loci has proven to be complicated. Transcriptome-wide association studies (TWAS) providing a powerful approach to identify novel disease risk genes and uncover possible causal genes at loci identified previously by GWAS. However, these methods did not consider the importance of epigenetic regulation in gene expression. Here, we developed a novel epigenetic element-based transcriptome-wide association study (ETWAS) that tests the effects of genetic variants on gene expression levels with the epigenetic features as prior and further mediates the association between predicted expression and BD. We conducted an ETWAS consisting of 20,352 cases and 31,358 controls and identified 44 transcriptome-wide significant hits. We found 14 conditionally independent genes, and 11 did not previously implicate with BD, which regarded as novel candidate genes, such as ASB16 in the cerebellar hemisphere ( P = 9.29×10 −8 ). We demonstrated that several genome-wide significant signals from the BD GWAS driven by genetically regulated expression, and conditioning of NEK4 explaining 90.1% of the GWAS signal. Additionally, ETWAS identified genes could explain heritability beyond that explained by GWAS-associated SNPs ( P = 0.019). In conclusion, ETWAS is a powerful method, and we identified several novel candidate genes associated with BD." @default.
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• W3044338046 date "2020-07-24" @default.
• W3044338046 modified "2023-10-16" @default.
• W3044338046 title "Epigenetic Element-Based Transcriptome-Wide Association Study Identifies Novel Genes for Bipolar Disorder" @default.
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• W3044338046 doi "https://doi.org/10.1101/2020.07.23.20161174" @default.
• W3044338046 hasPublicationYear "2020" @default.
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