Timothy Vyse, Yong Cui, Wanling Yang and colleagues report a meta-analysis of genome-wide association studies for systemic lupus erythematosus (SLE) including European and Chinese individuals. They identify ten new loci associated with SLE and find evidence for increased genetic risk of disease among individuals of non-European ancestry. Systemic lupus erythematosus (SLE; OMIM 152700) is a genetically complex autoimmune disease. Genome-wide association studies (GWASs) have identified more than 50 loci as robustly associated with the disease in single ancestries, but genome-wide transancestral studies have not been conducted. We combined three GWAS data sets from Chinese (1,659 cases and 3,398 controls) and European (4,036 cases and 6,959 controls) populations. A meta-analysis of these studies showed that over half of the published SLE genetic associations are present in both populations. A replication study in Chinese (3,043 cases and 5,074 controls) and European (2,643 cases and 9,032 controls) subjects found ten previously unreported SLE loci. Our study provides further evidence that the majority of genetic risk polymorphisms for SLE are contained within the same regions across both populations. Furthermore, a comparison of risk allele frequencies and genetic risk scores suggested that the increased prevalence of SLE in non-Europeans (including Asians) has a genetic basis.

Objective Systemic lupus erythematosus (SLE), an autoimmune disorder, has been associated with nearly 100 susceptibility loci. Nevertheless, these loci only partially explain SLE heritability and their putative causal variants are rarely prioritised, which make challenging to elucidate disease biology. To detect new SLE loci and causal variants, we performed the largest genome-wide meta-analysis for SLE in East Asian populations. Methods We newly genotyped 10 029 SLE cases and 180 167 controls and subsequently meta-analysed them jointly with 3348 SLE cases and 14 826 controls from published studies in East Asians. We further applied a Bayesian statistical approach to localise the putative causal variants for SLE associations. Results We identified 113 genetic regions including 46 novel loci at genome-wide significance (p<5×10⁻⁸). Conditional analysis detected 233 association signals within these loci, which suggest widespread allelic heterogeneity. We detected genome-wide associations at six new missense variants. Bayesian statistical fine-mapping analysis prioritised the putative causal variants to a small set of variants (95% credible set size ≤10) for 28 association signals. We identified 110 putative causal variants with posterior probabilities ≥0.1 for 57 SLE loci, among which we prioritised 10 most likely putative causal variants (posterior probability ≥0.8). Linkage disequilibrium score regression detected genetic correlations for SLE with albumin/globulin ratio (r_g=−0.242) and non-albumin protein (r_g=0.238). Conclusion This study reiterates the power of large-scale genome-wide meta-analysis for novel genetic discovery. These findings shed light on genetic and biological understandings of SLE.

Systemic lupus erythematosus (SLE) is an autoimmune disease with heterogeneous clinical manifestations influenced by genetic and environmental factors. Five novel susceptibility genes (TNIP1, SLC15A4, ETS1, RasGRP3 and IKZF1) for SLE have been identified in a recent genome-wide association study of a Chinese Han population. This study investigated their relationships with disease subphenotypes, including renal nephritis, photosensitivity, antinuclear antibody (ANA), age at diagnosis, malar rash, discoid rash, immunological disorder, oral ulcer, hematological disorder, neurological disorder, serositis, arthritis and vasculitis. Significant associations were found for the single nucleotide polymorphism rs10036748 of TNIP1 with photosensitivity (odds ratio (OR) = 0.87, p = 0.01) and vasculitis (OR = 1.18, p = 0.04); rs10847697 of SLC15A4 with discoid rash (OR = 1.18, p = 0.02); rs6590330 of ETS1 with SLE of age at diagnosis <20 years (OR = 1.24, p = 8.91 × 10^-5); rs13385731 of RasGRP3 with malar rash (OR = 1.20, p = 0.01), discoid rash (OR = 0.78, p = 0.02) and ANA (OR = 0.72, p = 0.004); rs4917014 of IKZF1 with renal nephritis (OR = 1.13, p = 0.02) and malar rash (OR = 0.83, p = 0.00038), respectively. The study suggested that these susceptibility genes might not only play important roles in the development of SLE, but also contribute to the complex phenotypes of SLE. Lupus (2010) 19, 1181—1186.

Background: Genome-wide association studies (GWASs) have revealed a large number of genetic risk loci for many autoimmune diseases. One clear finding emerging from the published genetic studies of autoimmunity is that different autoimmune diseases, such as psoriasis and systemic lupus erythematosus (SLE), share susceptibility loci. Our study explores additional susceptibility loci shared by psoriasis and SLE in the Chinese Han population. Methods: In total, 20 single nucleotide polymorphisms (SNPs) in 17 previously reported psoriasis susceptibility loci and 34 SNPs from 24 previously reported SLE susceptibility loci were investigated in our initial psoriasis and SLE GWAS dataset. Among these SNPs, we selected two SNPs (rs8016947 and rs4649203) with association values of p<5×10⁻² for both diseases in the GWAS data for further investigation in psoriasis (7260 cases and 9842 controls) and SLE (2207 cases and 9842 controls) using a Sequenom MassARRAY system. Results: We found that these two SNPs (rs8016947 and rs4649203) in two loci (NFKBIA and IL28RA) were associated with psoriasis and SLE with genome-wide significance (P_combined<5×10⁻⁸ in psoriasis and P_combined<5×10⁻⁸ in SLE): rs8016947 at NFKBIA (P_combined-psoriasis=3.90×10⁻¹⁰, P_combined-SLE=1.08×10⁻¹³) and rs4649203 at IL28RA (P_combined-psoriasis=3.91×10⁻¹², P_combined-SLE=9.90×10⁻⁹). Conclusions: These results showed that two common susceptibility loci (NFKBIA and IL28RA) are shared by psoriasis and SLE in the Chinese Han population.