Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Meta-Analysis of Autoimmune Variants Shared between Systemic Lupus Erythematosus (SLE) and 16 Other Diseases Identifies Novel SLE Loci.
Ramos3, Paula S., Gaffney1, Patrick M., Criswell12, Lindsey A., Comeau3, Mary E., Williams3, Adrienne H., Graham8, Robert R., Chung10, Sharon A.
Arthritis and Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK
Rosalind Russell Medical Research Center for Arthritis, University of California, San Francisco, San Francisco, CA
UCLA School of Medicine, Los Angeles, CA
UCSF-Box 0500, San Francisco, CA
Univ of OK Hlth Sci Ctr, Oklahoma City, OK
Arthritis and Immunology Program, Oklahoma Medical Research Foundation
Dept Biostatistical Sciences, Wake Forest University Health Sciences
Dept Medicine, University of Alabama at Birmingham, Birmingham, AL
Dept of Cell Biology and Neuroscience, University of California, Riverside
Dept of Genetics and Pathology, Uppsala University, Uppsala, Sweden
Faculty of Medicine, Imperial College, London, UK
Immunology Biomarkers Group, Genentech
Keck School of Medicine, University of Southern California, Los Angeles, Los Angeles, CA
The clustering of multiple autoimmune disorders (ADs) in families is well known. Nevertheless, evidence of specific shared variants is sparse, and consequently the genetic mechanisms that may explain the patterns of disease aggregation remain unclear. This study is aimed at assessing which variants are common and different between SLE and other ADs. As such, we compared the variants reported as associated in genome-wide association studies (GWAS) of ADs to those identified in our large-scale analysis of SLE. We compiled a list with 381 non-MHC variants identified as significant in 49 GWAS of 16 ADs, available at the GWAS catalog (www.genome.gov/gwastudies). We combined the genotypic and imputed data from three published Caucasian cohorts (total of 1500 cases and 5706 controls)(Seligman et al, 2001; Remmers et al, 2007; Graham et al, 2008; Harley et al, 2008) and performed a joint- and a meta-analysis. When available, we used data from a previously described independent replication cohort of 2085 SLE cases and 2854 controls (Harley et al, 2008). All analyses were adjusted for admixture. Of the 213 SNPs that met quality control criteria, 44 survived a multiple comparisons adjustment with P<0.05 in the joint-analysis. Interestingly, the loci most shared between GWAS of ADs include IL23R, TNFAIP3, PTPN22, IL12B, IL12RA and PFKFB3-PRKCQ. Based on the number of genome-wide significant loci, we observe that SLE shares the most loci with Crohn's disease (TNFAIP3, ATG5, and 7p12.2), followed by both rheumatoid arthritis (TNFAIP3, BLK) and psoriasis (TNFAIP3, TNIP1), reflecting the number of published GWAS and associated SNPs available from the GWAS catalog. Several autoimmune variants were herein confirmed to be associated with SLE. These include SNPs in the TNFAIP3 (rs2230926, P=1.39×1020; rs5029939, P=1.51×1014; rs6920220, P=5.34×10-06), BLK (rs2736340, P=3.59×10-07; rs2618476, P=1.10×10-07), IL10 (rs3024505, P=6.45×10-05; rs3024493, P=4.38×10-05), and TYK2 (rs2304256, P=2.44×10-08) regions. Novel SLE loci include the VTCN1 (rs12046117, P=2.02×10-06), CD40 (rs1569723 P=1.26×10-03), IRGM (rs11747270, P=1.12×10-03) and IL12A (rs4680534, P=1.78×10-03) regions. This study expands the number of candidate loci associated with SLE and further dissects the extent of genetic overlap between SLE and other ADs.
To cite this abstract, please use the following information:
Ramos, Paula S., Gaffney, Patrick M., Criswell, Lindsey A., Comeau, Mary E., Williams, Adrienne H., Graham, Robert R., et al; Meta-Analysis of Autoimmune Variants Shared between Systemic Lupus Erythematosus (SLE) and 16 Other Diseases Identifies Novel SLE Loci. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :500