UBE2W Improves the Experimental Colitis by Inhibiting the NF-κB Signaling Pathway

Wang, Shaoxin; Pu, Jun; Li, Xiaowei; Yan, Zhihui; Li, Chao; Zheng, Yan; Luo, Zhe; Cui, Lihong

doi:10.1007/s10620-022-07453-4

Cited by 3 publications

(2 citation statements)

References 30 publications

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“…Ubiquitination is a post-translational modification that controls multiple steps in autophagy, a key process implicated in IBD. Indeed, UBE2W knockdown mice showed mucosal injuries, and its overexpression ameliorated the severity of experimental colitis, a model of IBD 46 .…”

Section: Resultsmentioning

confidence: 99%

Adjusting for genetic confounders in transcriptome-wide association studies improves discovery of risk genes of complex traits

Zhao,

Crouse,

Qian

et al. 2024

Nat Genet

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Many methods have been developed to leverage expression quantitative trait loci (eQTL) data to nominate candidate genes from genome-wide association studies. These methods, including colocalization, transcriptome-wide association studies (TWAS) and Mendelian randomization-based methods; however, all suffer from a key problem—when assessing the role of a gene in a trait using its eQTLs, nearby variants and genetic components of other genes’ expression may be correlated with these eQTLs and have direct effects on the trait, acting as potential confounders. Our extensive simulations showed that existing methods fail to account for these ‘genetic confounders’, resulting in severe inflation of false positives. Our new method, causal-TWAS (cTWAS), borrows ideas from statistical fine-mapping and allows us to adjust all genetic confounders. cTWAS showed calibrated false discovery rates in simulations, and its application on several common traits discovered new candidate genes. In conclusion, cTWAS provides a robust statistical framework for gene discovery.

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Section: Resultsmentioning

confidence: 99%

Adjusting for genetic confounders in transcriptome-wide association studies improves discovery of risk genes of complex traits

Zhao,

Crouse,

Qian

et al. 2024

Nat Genet

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show abstract

“…Ubiquitination is a post-translational modification that controls multiple steps in autophagy, a key process implicated in IBD [41]. Indeed, UBE2W knockdown mice showed mucosal injuries, and its overexpression ameliorated the severity of experimental colitis, a model of IBD [42].…”

Section: Resultsmentioning

confidence: 99%

Adjusting for genetic confounders in transcriptome-wide association studies leads to reliable detection of causal genes

Zhao

Crouse

Qian

et al. 2022

Preprint

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Expression QTLs (eQTLs), provide valuable information on the functional effects of variants. Many methods have been developed to leverage eQTLs to nominate candidate genes of complex traits. These methods include colocalization analysis, transcriptome-wide association studies (TWAS) that correlate genetic components of expression with traits, and Mendelian Randomization (MR)-based methods. A fundamental problem of all these methods is that, when assessing the role of one gene in a trait using its eQTLs, nearby variants and nearby genetic components of expression of other genes can be correlated with the eQTLs of the test gene, while affecting the trait directly. These "genetic confounders" may lead to false discoveries. To address this challenge, we introduced a novel statistical framework that generalizes TWAS to adjust all genetic confounders. In our simulations, we found that existing methods based on TWAS, colocalization or MR all suffered from high false positive rates, often greater than 50%. Our method, causal-TWAS (cTWAS), in contrast, showed calibrated false positive rates while maintaining power. Application of cTWAS on several common traits highlighted the weakness of existing methods and discovered novel candidate genes. In conclusion, cTWAS is a robust statistical framework to integrate eQTL and GWAS data for gene discovery, and is extendable to other molecular QTLs.

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Large-scale cross-trait genetic analysis highlights shared genetic backgrounds of autoimmune diseases

Yamamoto,

Shirai,

Edahiro

et al. 2024

Immunological Medicine

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UBE2W Improves the Experimental Colitis by Inhibiting the NF-κB Signaling Pathway

Cited by 3 publications

References 30 publications

Adjusting for genetic confounders in transcriptome-wide association studies improves discovery of risk genes of complex traits

Adjusting for genetic confounders in transcriptome-wide association studies improves discovery of risk genes of complex traits

Adjusting for genetic confounders in transcriptome-wide association studies leads to reliable detection of causal genes

Large-scale cross-trait genetic analysis highlights shared genetic backgrounds of autoimmune diseases

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