ArticleArthritis research & therapy2021
Single-cell expression quantitative trait loci (eQTL) analysis of SLE-risk loci in lupus patient monocytes.
Article in Arthritis research & therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 11 citations in OpenAlex.
- Systemic lupus erythematosus genetics: insights into pathogenesis and implications for therapy.Nature reviews. Rheumatology · 2024Review
- Cromolyn prevents cerebral vasospasm and dementia by targeting WDR43.Frontiers in aging neuroscience · 2023Article
- Systemic blockade of proBDNF inhibited the expansion and altered the transcriptomic expression in CD3Lupus science & medicine · 2022Article
- Study on the Relationship between lncRNA Gene Polymorphism and Systemic Lupus Erythematosus.Computational and mathematical methods in medicine · 2022Article
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Authors and funding
16 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundWe performed expression quantitative trait locus (eQTL) analysis in single classical (CL) and non-classical (NCL) monocytes from patients with systemic lupus erythematosus (SLE) to quantify the impact of well-established genetic risk alleles on transcription at single-cell resolution.
methodsSingle-cell gene expression was quantified using qPCR in purified monocyte subpopulations (CD14
resultsThe SLE-risk alleles demonstrated significantly more eQTLs in NCLs as compared to CLs (p = 0.0004). There were 18 eQTLs exclusive to NCL cells, 5 eQTLs exclusive to CL cells, and only one shared eQTL, supporting large differences in the impact of the risk alleles between these monocyte subsets. The SPP1 and TNFAIP3 loci were associated with the greatest number of transcripts. Patterns of shared influence in which different SNPs impacted the same transcript also differed between monocyte subsets, with greater evidence for synergy in NCL cells. IRF1 expression demonstrated an on/off pattern, in which expression was zero in all of the monocytes studied from some individuals, and this pattern was associated with a number of SLE risk alleles. We observed corroborating evidence of this IRF1 expression pattern in public data sets.
conclusionsWe document multiple SLE-risk allele eQTLs in single monocytes which differ greatly between CL and NCL subsets. These data support the importance of the SPP1 and TNFAIP3 risk variants and the IRF1 transcript in SLE patient monocyte function.
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