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Transcriptome-wide ...
Transcriptome-wide association analysis of brain structures yields insights into pleiotropy with complex neuropsychiatric traits
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Zhao, BX (författare)
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Shan, Y (författare)
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Yang, Y (författare)
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Yu, ZL (författare)
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Li, TF (författare)
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Wang, XF (författare)
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Luo, TY (författare)
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Zhu, ZL (författare)
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- Sullivan, P (författare)
- Karolinska Institutet
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Zhao, HY (författare)
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Li, Y (författare)
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Zhu, HT (författare)
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(creator_code:org_t)
- 2021-05-17
- 2021
- Engelska.
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 2878-
- Relaterad länk:
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https://www.nature.c...
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http://kipublication...
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https://doi.org/10.1...
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Abstract
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- Structural variations of the human brain are heritable and highly polygenic traits, with hundreds of associated genes identified in recent genome-wide association studies (GWAS). Transcriptome-wide association studies (TWAS) can both prioritize these GWAS findings and also identify additional gene-trait associations. Here we perform cross-tissue TWAS analysis of 211 structural neuroimaging and discover 278 associated genes exceeding Bonferroni significance threshold of 1.04 × 10−8. The TWAS-significant genes for brain structures have been linked to a wide range of complex traits in different domains. Through TWAS gene-based polygenic risk scores (PRS) prediction, we find that TWAS PRS gains substantial power in association analysis compared to conventional variant-based GWAS PRS, and up to 6.97% of phenotypic variance (p-value = 7.56 × 10−31) can be explained in independent testing data sets. In conclusion, our study illustrates that TWAS can be a powerful supplement to traditional GWAS in imaging genetics studies for gene discovery-validation, genetic co-architecture analysis, and polygenic risk prediction.
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- Av författaren/redakt...
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Zhao, BX
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Shan, Y
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Yang, Y
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Yu, ZL
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Li, TF
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Wang, XF
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visa fler...
-
Luo, TY
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Zhu, ZL
-
Sullivan, P
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Zhao, HY
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Li, Y
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Zhu, HT
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visa färre...
- Artiklar i publikationen
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Nature communica ...
- Av lärosätet
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Karolinska Institutet