Single-cell expression quantitative trait loci (eQTL) analysis of SLE-risk loci in lupus patient monocytes

Abstract Background We 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 resolu...

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Autores principales:	Yogita Ghodke-Puranik, Zhongbo Jin, Kip D. Zimmerman, Hannah C. Ainsworth, Wei Fan, Mark A. Jensen, Jessica M. Dorschner, Danielle M. Vsetecka, Shreyasee Amin, Ashima Makol, Floranne Ernste, Thomas Osborn, Kevin Moder, Vaidehi Chowdhary, Carl D. Langefeld, Timothy B. Niewold
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Diseases of the musculoskeletal system RC925-935
Acceso en línea:	https://doaj.org/article/96e352fc33f345cd81032036828010a0
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spelling	oai:doaj.org-article:96e352fc33f345cd81032036828010a02021-12-05T12:04:45ZSingle-cell expression quantitative trait loci (eQTL) analysis of SLE-risk loci in lupus patient monocytes10.1186/s13075-021-02660-21478-6362https://doaj.org/article/96e352fc33f345cd81032036828010a02021-11-01T00:00:00Zhttps://doi.org/10.1186/s13075-021-02660-2https://doaj.org/toc/1478-6362Abstract Background We 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. Methods Single-cell gene expression was quantified using qPCR in purified monocyte subpopulations (CD14++CD16− CL and CD14dimCD16+ NCL) from SLE patients. Novel analysis methods were used to control for the within-person correlations observed, and eQTLs were compared between cell types and risk alleles. Results The 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. Conclusions We 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.Yogita Ghodke-PuranikZhongbo JinKip D. ZimmermanHannah C. AinsworthWei FanMark A. JensenJessica M. DorschnerDanielle M. VseteckaShreyasee AminAshima MakolFloranne ErnsteThomas OsbornKevin ModerVaidehi ChowdharyCarl D. LangefeldTimothy B. NiewoldBMCarticleDiseases of the musculoskeletal systemRC925-935ENArthritis Research & Therapy, Vol 23, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Diseases of the musculoskeletal system RC925-935
spellingShingle	Diseases of the musculoskeletal system RC925-935 Yogita Ghodke-Puranik Zhongbo Jin Kip D. Zimmerman Hannah C. Ainsworth Wei Fan Mark A. Jensen Jessica M. Dorschner Danielle M. Vsetecka Shreyasee Amin Ashima Makol Floranne Ernste Thomas Osborn Kevin Moder Vaidehi Chowdhary Carl D. Langefeld Timothy B. Niewold Single-cell expression quantitative trait loci (eQTL) analysis of SLE-risk loci in lupus patient monocytes
description	Abstract Background We 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. Methods Single-cell gene expression was quantified using qPCR in purified monocyte subpopulations (CD14++CD16− CL and CD14dimCD16+ NCL) from SLE patients. Novel analysis methods were used to control for the within-person correlations observed, and eQTLs were compared between cell types and risk alleles. Results The 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. Conclusions We 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.
format	article
author	Yogita Ghodke-Puranik Zhongbo Jin Kip D. Zimmerman Hannah C. Ainsworth Wei Fan Mark A. Jensen Jessica M. Dorschner Danielle M. Vsetecka Shreyasee Amin Ashima Makol Floranne Ernste Thomas Osborn Kevin Moder Vaidehi Chowdhary Carl D. Langefeld Timothy B. Niewold
author_facet	Yogita Ghodke-Puranik Zhongbo Jin Kip D. Zimmerman Hannah C. Ainsworth Wei Fan Mark A. Jensen Jessica M. Dorschner Danielle M. Vsetecka Shreyasee Amin Ashima Makol Floranne Ernste Thomas Osborn Kevin Moder Vaidehi Chowdhary Carl D. Langefeld Timothy B. Niewold
author_sort	Yogita Ghodke-Puranik
title	Single-cell expression quantitative trait loci (eQTL) analysis of SLE-risk loci in lupus patient monocytes
title_short	Single-cell expression quantitative trait loci (eQTL) analysis of SLE-risk loci in lupus patient monocytes
title_full	Single-cell expression quantitative trait loci (eQTL) analysis of SLE-risk loci in lupus patient monocytes
title_fullStr	Single-cell expression quantitative trait loci (eQTL) analysis of SLE-risk loci in lupus patient monocytes
title_full_unstemmed	Single-cell expression quantitative trait loci (eQTL) analysis of SLE-risk loci in lupus patient monocytes
title_sort	single-cell expression quantitative trait loci (eqtl) analysis of sle-risk loci in lupus patient monocytes
publisher	BMC
publishDate	2021
url	https://doaj.org/article/96e352fc33f345cd81032036828010a0
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Single-cell expression quantitative trait loci (eQTL) analysis of SLE-risk loci in lupus patient monocytes

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