Causal association of monocytes with chronic kidney disease and the mediation role of frailty: A study integrating large-scale two-sample Mendelian randomization and single-cell analysis

Zhang, Cong; Deng, Jielian; Li, Kangjie; Lai, Guichuan; Liu, Hui; Zhang, Yuan; Zeng, Haijiao; Li, Wenlong; Zhong, Xiaoni; Wang, Yao; Xie, Biao

doi:10.1016/j.archger.2024.105435

Cited by 1 publication

(1 citation statement)

References 42 publications

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“…This goes beyond simple GWAS. With this method, some researches were conducted such as chronic kidney disease ( 25 ), gout ( 26 ) and Atherosclerosis ( 27 ).…”

Section: Discussionmentioning

confidence: 99%

Integrated analyses of single-cell transcriptome and Mendelian randomization reveal the protective role of FCRL3 in multiple sclerosis

Yu,

Jiang,

et al. 2024

Front. Immunol.

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BackgroundMultiple sclerosis (MS) represents a multifaceted autoimmune ailment, prompting the development and widespread utilization of numerous therapeutic interventions. However, extant medications for MS have proven inadequate in mitigating relapses and halting disease progression. Innovative drug targets for preventing multiple sclerosis are still required. The objective of this study is to discover novel therapeutic targets for MS by integrating single-cell transcriptomics and Mendelian randomization analysis.MethodsThe study integrated MS genome-wide association study (GWAS) data, single-cell transcriptomics (scRNA-seq), expression quantitative trait loci (eQTL), and protein quantitative trait loci (pQTL) data for analysis and utilized two-sample Mendelian randomization study to comprehend the causal relationship between proteins and MS. Sequential analyses involving colocalization and Phenome-wide association studies (PheWAS) were conducted to validate the causal role of candidate genes.ResultsFollowing stringent quality control preprocessing of scRNA-seq data, 1,123 expression changes across seven peripheral cell types were identified. Among the seven most prevalent cell types, 97 genes exhibiting at least one eQTL were discerned. Examination of MR associations between 28 proteins with available index pQTL signals and the risk of MS outcomes was conducted. Co-localization analyses and PheWAS indicated that FCRL3 may exert influence on MS.ConclusionThe integration of scRNA-seq and MR analysis facilitated the identification of potential therapeutic targets for MS. Notably, FCRL3, implicated in immune function, emerged as a significant drug target in the deCODE databases. This research underscores the importance of FCRL3 in MS therapy and advocates for further investigation and clinical trials targeting FCRL3.

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“…This goes beyond simple GWAS. With this method, some researches were conducted such as chronic kidney disease ( 25 ), gout ( 26 ) and Atherosclerosis ( 27 ).…”

Section: Discussionmentioning

confidence: 99%

Integrated analyses of single-cell transcriptome and Mendelian randomization reveal the protective role of FCRL3 in multiple sclerosis

Yu,

Jiang,

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

show abstract

Causal association of monocytes with chronic kidney disease and the mediation role of frailty: A study integrating large-scale two-sample Mendelian randomization and single-cell analysis

Cited by 1 publication

References 42 publications

Integrated analyses of single-cell transcriptome and Mendelian randomization reveal the protective role of FCRL3 in multiple sclerosis

Integrated analyses of single-cell transcriptome and Mendelian randomization reveal the protective role of FCRL3 in multiple sclerosis

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