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.
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 August 3, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-new-susceptibility-locus-for-systemic-lupus-erythematosus-on-chromosome-12/