ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 108

A New Susceptibility Locus for Systemic Lupus Erythematosus on Chromosome 12

F. Yesim Demirci1, Xingbin Wang1, Jennifer A. Kelly2, David L. Morris3, M. Michael Barmada1, Eleanor Feingold1, Amy H. Kao4, Kathy L. Sivils5, Sasha Bernatsky6, Christian A. Pineau6, Ann Clarke7, Rosalind Ramsey-Goldman8, Timothy Vyse9, Patrick M. Gaffney10, Susan Manzi11 and M. Ilyas Kamboh12, 1Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, 2Arthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, 3Department of Medical & Molecular Genetics, King's College London, London, United Kingdom, 4Lupus Center of Excellence, Department of Medicine, West Penn Allegheny Health System, Pittsburgh, PA, 5Oklahoma Medical Research Foundation, Oklahoma City, OK, 6Divisions of Rheumatology and Clinical Epidemiology, McGill University Health Centre, Montreal, QC, Canada, 7Division of Rheumatology, Department of Medicine, University of Calgary, Calgary, AB, Canada, 8Northwestern University Feinberg School of Medicine, Chicago, IL, 9Division of Genetics and Molecular Medicine and Division of Immunology, Infection and Inflammatory Disease, King's College London, London, United Kingdom, 10Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, 11Internal Medicine, West Penn Allegheny Health System, Pittsburgh, PA, 12Human Genetics, University of Pittsburgh, Pittsburgh, PA

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: ,

Session Information

Date: Sunday, November 8, 2015

Session Title: Genetics, Genomics and Proteomics Poster I

Session Type: ACR Poster Session A

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

Background/Purpose: Genome-wide association studies (GWASs) and large follow-up studies in European-descent or Asian subjects have identified a number of susceptibility loci for systemic lupus erythematosus (SLE) to date. Despite this tremendous progress, a significant portion of genetic component of SLE still remains to be uncovered. The purpose of this multi-stage study was to identify new susceptibility loci for SLE in individuals of European ancestry.

Methods: In Stage 1, a new GWAS of SLE was conducted in a North American case-control sample of European ancestry (~1,200 subjects) genotyped on Affymetrix Genome-Wide Human SNP Array 6.0. In Stage 2, the top new suggestive GWAS hits were further investigated by in silico evaluation in an additional dataset of European-descent subjects (>2,500 individuals) followed by meta-analysis. In Stage 3, the top meta-analysis findings were evaluated for replication in another dataset of European-descent subjects (>10,000 individuals).

Results: Our GWAS revealed the most significant associations at the major histocompatibility complex (MHC) locus on chromosome 6p21 (P<5×10-8), followed by those on chromosomes 2q32 (STAT4) and 8p23 (BLK). Several other SLE signals/loci previously reported in Caucasians and/or Asians were also confirmed in our Stage 1 sample. Stage 2 meta-analyses identified a new genome-wide significant locus on chromosome 12q12 (meta P=3.1×10-8), which was replicated in Stage 3.

Conclusion: We conducted a new GWAS of SLE and, through a multi-stage approach, we have discovered and replicated a new SLE locus at 12q12. Publicly available databases suggest that this new SLE signal falls within a genomic region with regulatory function and near biologically relevant genes.

Disclosure: F. Y. Demirci, None; X. Wang, None; J. A. Kelly, None; D. L. Morris, None; M. M. Barmada, None; E. Feingold, None; A. H. Kao, None; K. L. Sivils, None; S. Bernatsky, None; C. A. Pineau, None; A. Clarke, None; R. Ramsey-Goldman, None; T. Vyse, None; P. M. Gaffney, None; S. Manzi, None; M. I. Kamboh, None.

To cite this abstract in AMA style:

Demirci FY, Wang X, Kelly JA, Morris DL, Barmada MM, Feingold E, Kao AH, Sivils KL, Bernatsky S, Pineau CA, Clarke A, Ramsey-Goldman R, Vyse T, Gaffney PM, Manzi S, Kamboh MI. A New Susceptibility Locus for Systemic Lupus Erythematosus on Chromosome 12 [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/a-new-susceptibility-locus-for-systemic-lupus-erythematosus-on-chromosome-12/. Accessed April 10, 2020.

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