title: A genome-wide association study identified AFF1 as a susceptibility locus for systemic lupus eyrthematosus in Japanese.
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.
authors.affiliation: Laboratory for Autoimmune Diseases, Center for Genomic Medicine, RIKEN, Yokohama, Japan.
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Okada
authors.forename: Kenichi
authors.initials: K
authors.lastname: Shimane
authors.forename: Yuta
authors.initials: Y
authors.lastname: Kochi
authors.forename: Tomoko
authors.initials: T
authors.lastname: Tahira
authors.forename: Akari
authors.initials: A
authors.lastname: Suzuki
authors.forename: Koichiro
authors.initials: K
authors.lastname: Higasa
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takahashi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Horita
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Atsumi
authors.forename: Tomonori
authors.initials: T
authors.lastname: Ishii
authors.forename: Akiko
authors.initials: A
authors.lastname: Okamoto
authors.forename: Keishi
authors.initials: K
authors.lastname: Fujio
authors.forename: Michito
authors.initials: M
authors.lastname: Hirakata
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Amano
authors.forename: Yuya
authors.initials: Y
authors.lastname: Kondo
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ito
authors.forename: Kazuki
authors.initials: K
authors.lastname: Takada
authors.forename: Akio
authors.initials: A
authors.lastname: Mimori
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Saito
authors.forename: Makoto
authors.initials: M
authors.lastname: Kamachi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kawaguchi
authors.forename: Katsunori
authors.initials: K
authors.lastname: Ikari
authors.forename: Osman Wael
authors.initials: OW
authors.lastname: Mohammed
authors.forename: Koichi
authors.initials: K
authors.lastname: Matsuda
authors.forename: Chikashi
authors.initials: C
authors.lastname: Terao
authors.forename: Koichiro
authors.initials: K
authors.lastname: Ohmura
authors.forename: Keiko
authors.initials: K
authors.lastname: Myouzen
authors.forename: Naoya
authors.initials: N
authors.lastname: Hosono
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Tsunoda
authors.forename: Norihiro
authors.initials: N
authors.lastname: Nishimoto
authors.forename: Tsuneyo
authors.initials: T
authors.lastname: Mimori
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Matsuda
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Takayuki
authors.initials: T
authors.lastname: Sumida
authors.forename: Hisashi
authors.initials: H
authors.lastname: Yamanaka
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Takasaki
authors.forename: Takao
authors.initials: T
authors.lastname: Koike
authors.forename: Takahiko
authors.initials: T
authors.lastname: Horiuchi
authors.forename: Kenshi
authors.initials: K
authors.lastname: Hayashi
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kubo
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kamatani
authors.forename: Ryo
authors.initials: R
authors.lastname: Yamada
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamamoto
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007564:Japan; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D040641:Quantitative Trait Loci / Q000235:genetics*; D035602:Transcriptional Elongation Factors
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D035602:Transcriptional Elongation Factors; C081449:AFF1 protein, human