Genome-wide association meta-analysis in Chinese and European individuals identifies ten new loci associated with systemic lupus erythematosus

Abstract

Systemic lupus erythematosus (SLE; OMIM 1 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.

Confirmation of five novel susceptibility loci for Systemic Lupus Erythematosus (SLE) and integrated network analysis of 82 SLE susceptibility loci

“…We did not find significant heterogeneity of odds-ratios at most of the risk loci between Asian and European cohorts, consistent with published results (5,42). To understand the contribution of the loci to SLE inheritance, we estimated the percentage of explained heritability of 78 loci (four loci were monomorphic in Asians).…”

“…Additionally, we uncovered several novel loci that either fell just below genome-wide significance (P < 5Â10 À8 ) or were not independently replicated. In this follow-up study, we augmented our previous data with an additional cohort from Hong Kong and performed in silico replication together with published cohorts of European and Chinese descent (4,5). The added statistical power of the meta-analysis with nine cohorts allowed us to independently replicate five candidate loci above genome-wide significance.…”

“…The second set of data (in silico replication) for 5,057 Han Chinese (1,659 cases and 3,398 controls) and 11,022 Europeans (4,063 cases and 6,959 controls) was obtained as summary statistics from Morris et al (5). The third set of data was obtained from our previously published study of the SLE association in Asians (2), and included 17,140 individuals (4,478 cases and 12,656 controls) from six East Asian cohorts (Table 2).…”

“…To increase statistical power, we performed meta-analysis with in silico data from published Han Chinese and European cohorts (5). After combining these three cohorts, all five loci became significant (rs223881,…”

Identification of ST3AGL4, MFHAS1, CSNK2A2 and CD226 as loci associated with systemic lupus erythematosus (SLE) and evaluation of SLE genetics in drug repositioning

“…The current SLE GWAS were mainly performed in European and East Asian populations 6. Through combining GWAS from the two ethnicities, we recently identified 10 novel loci associated with SLE and uncovered a number of loci with suggestive association signal 6.…”