Integrative analysis of omics summary data reveals putative mechanisms linked to different cell populations in systemic lupus erythematosus
Systemic lupus erythematosus (SLE) is a complex disease involving many interactions at the molecular level, the details of which remain unclear. Here, we demonstrated an analytical paradigm of prioritizing genes and regulatory elements based on GWAS loci at the single-cell levels. Our initial step w...
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Veröffentlicht in: | Genomics (San Diego, Calif.) Calif.), 2022-07, Vol.114 (4), p.110435-110435, Article 110435 |
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Sprache: | eng |
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Zusammenfassung: | Systemic lupus erythematosus (SLE) is a complex disease involving many interactions at the molecular level, the details of which remain unclear. Here, we demonstrated an analytical paradigm of prioritizing genes and regulatory elements based on GWAS loci at the single-cell levels. Our initial step was to apply TWMR to identify causal genes and causal methylation sites in SLE. Based on the eQTL, LD and mQTL, we calculated the correlation between these genes and methylation sites. Next, we separately used gene expression and DNAm as exposure variables and outcome variables to analyze the regulatory mechanisms. We identified two mediating modes for SLE: 1) transcription mediation model and 2) epigenetic mediation model. Further, using single-cell RNA sequencing data, we revealed the cell subclusters associated with these mechanisms. Our identification of the mechanisms of SLE in different cell populations is of great significance for understanding the heterogeneity of disease in different cell populations.
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•The plausible mechanisms whereby the effect of a genetic variant on phenotype is mediated by genetic regulation of transcription/DNAm through DNAm/transcription are proposed.•The mechanism relies on specific cell subclusters.•An integrative analysis based on large-scale data lays the groundwork for resolving the origin of the SLE mechanisms. |
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ISSN: | 0888-7543 1089-8646 |
DOI: | 10.1016/j.ygeno.2022.110435 |