Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.

Evidence for Epistatic Gene-Gene Interactions in Systemic Lupus Erythematosus.

Hughes1,  Travis, Adler1,  Adam, Kelly1,  Jennifer A., Kaufman2,  Kenneth, Williams3,  Adrienne, Langefeld4,  Carl D., Elizabeth Brown for PROFILE,  

Oklahoma Medical Research Foundation, Oklahoma City, OK
Oklahoma Medical Research Foundation and Oklahoma University Health Sciences Center, Oklahoma City, OK
Divisions of Genetics and Molecular Medicine and Immunology, King's College London, London, United Kingdom
Oklahoma Medical Research Foundation, Center for Genomics and Oncological Research Pfizer-University of Granada-Junta de Andalucia, Oklahoma City, OK
Cincinnati Children's Hospital Medical Center and the US Department of Veterans Affairs Medical Center, Cincinnati, OH
University of Michigan, Ann Arbor, MI
Oklahoma Medical Research Foundation, Oklahoma CIty, OK
Wake Forest University, Winston-Salem
Wake Forest University Health Sciences, Winston-Salem, NC
Instituto de Parasitologia y Biomedicina Lopez-Neyra (CSIC), Granada, Spain
University of PuertoRico Medical Sciences Campus, San Juan, PR
Division of Rheumatologyand Immunology, Medical University of South Carolina, Charleston, SC
Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK


Several confirmed genetic susceptibility loci for lupus have been described. To date, no clear evidence for genetic epistasis is established in lupus. We test for gene-gene interactions in a number of known lupus susceptibility loci.


Eighteen SNPs tagging independent and confirmed lupus susceptibility loci were genotyped in a set of 4,250 lupus patients and 3,818 normal healthy controls of European descent. Epistasis was tested using a 2-step approach utilizing both a parametric and non-parametric (multifactor dimensionality reduction) methods. False discovery rate (FDR) was used to correct for multiple testing.


We detected and confirmed gene-gene interactions between HLA and CTLA4, HLA and IRF5, HLA and ITGAM, and PDCD1 and IL21 in lupus patients. The most significant interaction detected by parametric analysis was between rs3131379 in the HLA region and rs231775 in CTLA4 (P= 7.73×10-5 (FDR<=0.05), PMDR= 2.82×10-47).


We provide a strong evidence for gene-gene epistasis in systemic lupus erythematosus. These findings support a role for genetic interaction upon the complexity of lupus heritability.

To cite this abstract, please use the following information:
Hughes, Travis, Adler, Adam, Kelly, Jennifer A., Kaufman, Kenneth, Williams, Adrienne, Langefeld, Carl D., et al; Evidence for Epistatic Gene-Gene Interactions in Systemic Lupus Erythematosus. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :150

Abstract Supplement

Meeting Menu