Genome-wide association studies in Hong Kong identified novel susceptibility genes for systemic lupus erythematosus

Poster - Session: Genomics: Program no. 1908Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with complex genetic inheritance. GWAS have identified a number of susceptibility genes for SLE in the last two years. However, the imbalance of the populations studied may have hindered our ability to detect susceptibility genes that are either population specific, or show differences in allele frequencies or linkage disequilibrium. We have conducted GWAS on 620 SLE patients collected in Hong Kong and 2193 controls matched by ethnicity and geography. Replication on 200 selected SNPs on independent sample collections from Hong Kong, Anhui, China, and Bangkok Thailand identified novel susceptibility genes for SLE include ELF1, CD247, and others. We present detailed data on CD247 below. Recently, CD247 (CD3Z) was found to be associated with SLE in populations of Caucasian in associated studies of small sample size. Our GWAS data from Chinese living in Hong Kong identified SNPs in and around CD247 to be associated with SLE risk. Two most significant SNPs were selected for further replication in 3180 Asian patients from Hong Kong, Mainland China, and Thailand, as well as 4626 ethnically- and geographically-matched controls. We confirmed the association of CD247 with SLE in Asian populations (rs704853, odds ratio (OR) = 0. 82, P = 7. 31 x 10-6; rs858543, OR = 1. 104, P = 0.0048). Subphenotype analysis showed that rs704853 is also linked to oral ulcer (OR = 0. 78, P = 0. 047), hematologic disorder (OR = 0. 78, P = 0. 033) and anti-ds-DNA antibody (OR = 0. 76, P = 0. 028). Understanding of the involvement of CD247 in the disease could shed new light on SLE mechanisms and help with development of new treatment paradigms.The 60th Annual Meeting of the American Society of Human Genetics (ASHG 2010), Washington, D.C., 2-6 November 2010