ELF1 is associated with systemic lupus erythematosus in Asian populations

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease with a strong genetic involvement. The susceptibility genes identified so far can only explain a small proportion of disease heritability. Through a genome-wide association in a Hong Kong Chinese cohort and subsequent replication in two other Asian populations, with a total of 3164 patients and 4482 matched controls, we identified association of ELF1 (E74-like factor 1) with SLE (rs7329174, OR = 1.26, joint P= 1.47 × 10(-8)). ELF1 belongs to the ETS family of transcription factors and is known to be involved in T cell development and function. Database analysis revealed transcripts making use of three alternative exon1s for this gene. Near equivalent expression levels of distinct transcripts initiated from alternative exon1s were detected in peripheral blood mononuclear cells from both SLE patients and healthy controls. Although a direct association of rs7329174 with the three forms of transcripts for this gene was not detected, these findings support an important role of ELF1 in SLE susceptibility and suggest a potentially tight regulation for the expression of this gene.

Genetics of systemic lupus erythematosus and Sjögren's syndrome: an update

“…In addition, IL12A and CXCR5 were identified as new loci for Sjögren's syndrome susceptibility. Except for CXCR5, the majority of the genes identified in this study are well-known risk loci for SLE susceptibility [89] underscoring the close relationship between both diseases (Fig. 1).…”

Genome-wide association study of skin complex diseases

“…The ethnic and genetic heterogeneity may contribute to the susceptibility and complex clinical manifestation in SLE. Nine GWAS of SLE have been published, which identified more than 30 susceptibility genes or loci for SLE and confirmed some of genes found by candidate gene study [36][37][38][39][40][41][42][43][44]. These susceptibility genes for SLE included HLA [37][38][39][40]45], IRF5 [37][38][39][40]45], TNFAIP3 [37,40,45], BLK [37,39,40,45], STAT4 [37][38][39][40]45], ITGAM [38,39], PTPN22 [38,40], PHRF1 (also called KIAA1542) [38,40], TNFSF4 (also called OX40L) [38,40], BANK1 [36], PRDM1 [40,45], ATG5 [38,40], PTTG1 [38], PXK [38], FCGR2A [38], HIC2 …”

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

“…In recent years, understanding of SLE’s genetic etiology has been transformed by GWASs, with the largest study in Europeans3 (4,036 cases and 6,959 controls) finding evidence of association at 41 autosomal loci. Meanwhile, two published GWASs4,5 in Chinese populations and follow-up studies in Asians6–10 found association at 31 loci, 11 of which are not published for Europeans. Thus 52 SLE disease-susceptibility autosomal loci have been mapped by GWASs in these two populations.…”