Association analyses confirm five susceptibility loci for systemic lupus erythematosus in the Han Chinese population

Abstract

IntroductionSystemic lupus erythematosus (SLE) is a multisystem autoimmune disease. Currently, numerous genetic loci of SLE have been confirmed. Here we try to further explore additional genes contributing to SLE susceptibility in this study.MethodsForty nine single nucleotide polymorphisms (SNPs) with moderate-risk for SLE in previous study were genotyped in a large-scale replication study with a total of 3,522 cases and 8,252 controls using the Sequenom Massarray system. Association analyses were performed using logistic regression with gender or sample cohorts as a covariate through PLINK 1.07 software.ResultsThis replication effort confirmed five reported SLE susceptibility loci reaching genome-wide levels of significance (Pmeta <5.00 × 10−08): TNFSF4 (rs1418190, odds ratio (OR) = 0.81, Pmeta = 1.08 × 10−08; rs4916219, OR = 0.80, Pmeta = 7.77 × 10−09), IRF8 (rs2934498, OR = 1.25, Pmeta = 4.97 × 10−09), miR-146a (rs2431697, OR = 0.69, Pmeta = 1.15 × 10−22), CD44 (rs2732547, OR = 0.82, Pmeta = 1.55 × 10−11), and TMEM39A (rs12494314, OR = 0.84, Pmeta = 1.01 × 10−09). Further logistic regression analysis indicated that the genetic effects within TNFSF4 detected in this study are independent from our previously reported signals.ConclusionsThis study increases the number of established susceptibility loci for SLE in Han Chinese population and highlights the contribution of multiple variants of modest effect. Although further studies will be required to identify the causal alleles within these loci, the findings make a significant step forward in our understanding of the genetic contribution to SLE in Chinese population.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0602-9) contains supplementary material, which is available to authorized users.

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

“…To assess the extent to which genetic association with SLE was shared between the Chinese and European populations, we compared association results in the European GWAS3 with a meta-analysis of both Chinese GWASs, for SNPs published as associated in European3 and/or Chinese studies4,6–9. Association signals were declared as ‘shared’ between the Chinese and European populations if the SNP met any one of the following four criteria:

The locus had a published association in both Chinese and European studies at a genome-wide level of significance ( P < 5 × 10 −8 ).

The SNP was published only for Europeans but the association P value in the Chinese meta-analysis was significant (FDR < 0.01 across all SNPs in this group) and the direction of effect in all three GWASs was the same.

The SNP was published only in a Chinese study but the association P value in the European GWAS was significant (FDR < 0.01) and the direction of effect in all three GWASs was the same.

If the SNP failed to meet the requirements for either (2) or (3), we performed a gene-based test (applying the software KGG39–41) on genes within ±1 Mb of the published SNP.

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Genome‐wide differential expression reveals candidate genes involved in the pathogenesis of lupus and lupus nephritis

“…A glance through the literature indicates discrepancies in the genetic susceptibility to lupus among different ethnic populations . Remarkably limited overlap was detected in the risk genes identified by the current study comparative to those from genome‐wide association studies and these include tumor necrosis factor, interferons, integrin alpha and dead box protein families, signifying the role of inflammation and apoptosis in genetic predisposition to lupus. However, the molecular events underlying pathological transition of lupus to LN remains largely unidentified in the literature.…”

Genetic Profiles for Systemic Lupus Erythematosus in Han Chinese Population: From Genome-Wide Association Study to Exome-Wide Association Study

“…SNP rs2230926 of TNFAIP3 was strongly associated with SLE of Chinese Han and also associated with arthritis, antinuclear antibody, and other subphenotypes of SLE (Cai et al, 2010). Subsequently, we conducted a series of replication studies and genotypeephenotype analysis to find many new susceptibility variants or genes associated with SLE (He et al, 2010;Sheng et al, 2011Sheng et al, , 2015Wen et al, 2017;Zhu et al, 2015). 2.…”