RRC ID 77391
Author Okada Y, Shimane K, Kochi Y, Tahira T, Suzuki A, Higasa K, Takahashi A, Horita T, Atsumi T, Ishii T, Okamoto A, Fujio K, Hirakata M, Amano H, Kondo Y, Ito S, Takada K, Mimori A, Saito K, Kamachi M, Kawaguchi Y, Ikari K, Mohammed OW, Matsuda K, Terao C, Ohmura K, Myouzen K, Hosono N, Tsunoda T, Nishimoto N, Mimori T, Matsuda F, Tanaka Y, Sumida T, Yamanaka H, Takasaki Y, Koike T, Horiuchi T, Hayashi K, Kubo M, Kamatani N, Yamada R, Nakamura Y, Yamamoto K.
Title A genome-wide association study identified AFF1 as a susceptibility locus for systemic lupus eyrthematosus in Japanese.
Journal PLoS Genet
Abstract Systemic lupus erythematosus (SLE) is an autoimmune disease that causes multiple organ damage. Although recent genome-wide association studies (GWAS) have contributed to discovery of SLE susceptibility genes, few studies has been performed in Asian populations. Here, we report a GWAS for SLE examining 891 SLE cases and 3,384 controls and multi-stage replication studies examining 1,387 SLE cases and 28,564 controls in Japanese subjects. Considering that expression quantitative trait loci (eQTLs) have been implicated in genetic risks for autoimmune diseases, we integrated an eQTL study into the results of the GWAS. We observed enrichments of cis-eQTL positive loci among the known SLE susceptibility loci (30.8%) compared to the genome-wide SNPs (6.9%). In addition, we identified a novel association of a variant in the AF4/FMR2 family, member 1 (AFF1) gene at 4q21 with SLE susceptibility (rs340630; P = 8.3×10(-9), odds ratio = 1.21). The risk A allele of rs340630 demonstrated a cis-eQTL effect on the AFF1 transcript with enhanced expression levels (P<0.05). As AFF1 transcripts were prominently expressed in CD4(+) and CD19(+) peripheral blood lymphocytes, up-regulation of AFF1 may cause the abnormality in these lymphocytes, leading to disease onset.
Volume 8(1)
Pages e1002455
Published 2012-1-1
DOI 10.1371/journal.pgen.1002455
PMID 22291604
PMC PMC3266877
MeSH Adult Aged Alleles DNA-Binding Proteins / genetics* DNA-Binding Proteins / metabolism Female Gene Expression Genetic Predisposition to Disease Genome-Wide Association Study Genotype Humans Japan Lupus Erythematosus, Systemic / genetics* Lupus Erythematosus, Systemic / pathology Male Middle Aged Nuclear Proteins / genetics* Nuclear Proteins / metabolism Polymorphism, Single Nucleotide / genetics* Quantitative Trait Loci / genetics* Transcriptional Elongation Factors
IF 5.175
Human and Animal Cells CGM1(RCB0566)