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Single Cell Expression Quantitative Trait Loci (eqtl) Analysis of Established Systemic Lupus Erythematosus (sle)-risk Loci in Lupus Patient Monocytes

Friday, June 16
6:15 PM - 7:30 PM

Most confirmed SLE-risk loci are found near or in genes with immune function, yet how these loci influence diverse immune cell subsets remains unknown.  We performed single cell eQTL analysis in SLE monocytes to determine the impact of SLE-risk loci in single human monocytes. Purified classical (CL) and non-classical (NCL) monocytes from SLE patients were analyzed for expression of 90 genes, and patients were genotyped for 7 SLE-risk SNPs. Each monocyte subset was analyzed separately using non-parametric analyses. We observed a large number of significant eQTL associations that surpassed the 5% FDR. The SLE-associated SNPs demonstrated more eQTLs in NCLs as compared to CLs (p=2.5x10-8). For a given SNP, the eQTL associated transcripts differed between monocyte subsets (p < 0.001 for all 7 SNPs for discordance).  For NCLs, TNFAIP3, IRF5, IRF7, PTPN22, and SPP1 shared a significant proportion of eQTL associations. For CLs, TNFAIP3 shared many eQTLs with SPP1 and ITGAM, while SPP1 and ITGAM showed limited overlap. Thus, SLE-associated risk loci exert coordinated effects on gene expression within individual human monocytes, and the risk loci interact in different ways in different cell types. Our study revealed striking differences, using single cell gene expression, in the occurrence and interaction of SLE risk associated eQTLs within different but closely related cell types. This suggests pleiotropic effects from each locus across various immune cell types, and a high degree of complexity when considering how these loci impact the immune system.

Yogita Ghodke-Puranik

Assistant Professor
Department of Immunology and Division of Rheumatology, Mayo Clinic

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    Zhongbo Jin

    Department of Immunology and Division of Rheumatology, Mayo Clinic

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      Wei Fan

      Department of Rheumatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University

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        Mark Jensen

        Department of Immunology and Division of Rheumatology, Mayo Clinic

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          Jessica Dorschner

          Department of Immunology and Division of Rheumatology, Mayo Clinic

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            Danielle Vsetecka

            Department of Immunology and Division of Rheumatology, Mayo Clinic

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              Shreyasee Amin

              Associate Professor
              Division of Rheumatology, Mayo Clinic

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                Ashima Makol

                Assistant Professor
                Division of Rheumatology, Mayo Clinic

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                  Floranne Ernste

                  Assistant Professor
                  Division of Rheumatology, Mayo Clinic

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                    Thomas Osborn

                    Associate Professor
                    Division of Rheumatology, Mayo Clinic

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                      Kevin Moder

                      Associate Professor
                      Division of Rheumatology, Mayo Clinic

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                        Vaidehi Chowdhary

                        Assistant Professor
                        Division of Rheumatology, Mayo Clinic

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                          Timothy Niewold

                          Associate Professor
                          Department of Immunology and Division of Rheumatology, Mayo Clinic

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                            Single Cell Expression Quantitative Trait Loci (eqtl) Analysis of Established Systemic Lupus Erythematosus (sle)-risk Loci in Lupus Patient Monocytes



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