ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2657

Single Cell Expression Quantitative Trait Loci (eQTL) Analysis of Established Systemic Lupus Erythematosus (SLE)-Risk Loci in Lupus Patient Monocytes

Yogita Ghodke-Puranik1, Zhongbo Jin2, Wei Fan3, Mark A. Jensen1, Jessica M. Dorschner2, Danielle Vsetecka2, Shreyasee Amin4, Ashima Makol5, Floranne C. Ernste6, Thomas Osborn4, Kevin Moder4, Vaidehi Chowdhary7 and Timothy Niewold8, 1Colton Center for Autoimmunity, New York University, New York, NY, 2Division of Rheumatology and Department of Immunology, Mayo Clinic, Rochester, MN, 3Department of Rheumatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, China, Shanghai, China, 4Rheumatology, Mayo Clinic, Rochester, MN, 5Rheumatology, Mayo Clinic College of Medicine and Science, Rochester, MN, 6Division of Rheumatology, Mayo Clinic Rochester, Rochester, MN, 7Internal Medicine, Division of Rheumatology, Mayo Clinic College of Medicine and Science, Rochester, MN, 8New York University, New York, NY

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: ,

Session Information

Date: Tuesday, November 7, 2017

Title: Systemic Lupus Erythematosus – Human Etiology and Pathogenesis Poster II

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: 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.

Methods: 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.

Results: 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=2.5×10-8). 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.

Conclusion: 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.

Disclosure: Y. Ghodke-Puranik, None; Z. Jin, None; W. Fan, None; M. A. Jensen, None; J. M. Dorschner, None; D. Vsetecka, None; S. Amin, None; A. Makol, None; F. C. Ernste, None; T. Osborn, None; K. Moder, None; V. Chowdhary, None; T. Niewold, None.

To cite this abstract in AMA style:

Ghodke-Puranik Y, Jin Z, Fan W, Jensen MA, Dorschner JM, Vsetecka D, Amin S, Makol A, Ernste FC, Osborn T, Moder K, Chowdhary V, Niewold T. Single Cell Expression Quantitative Trait Loci (eQTL) Analysis of Established Systemic Lupus Erythematosus (SLE)-Risk Loci in Lupus Patient Monocytes [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/single-cell-expression-quantitative-trait-loci-eqtl-analysis-of-established-systemic-lupus-erythematosus-sle-risk-loci-in-lupus-patient-monocytes/. Accessed .

« Back to 2017 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/single-cell-expression-quantitative-trait-loci-eqtl-analysis-of-established-systemic-lupus-erythematosus-sle-risk-loci-in-lupus-patient-monocytes/