A genome-wide association study identified AFF1 as a susceptibility locus for systemic lupus eyrthematosus in Japanese

Yukinori Okada, Kenichi Shimane, Yuta Kochi, Tomoko Tahira, Akari Suzuki, Koichiro Higasa, Atsushi Takahashi, Tetsuya Horita, Tatsuya Atsumi, Tomonori Ishii, Akiko Okamoto, Keishi Fujio, Michito Hirakata, Hirofumi Amano, Yuya Kondo, Satoshi Ito, Kazuki Takada, Akio Mimori, Kazuyoshi Saito, Makoto KamachiYasushi Kawaguchi, Katsunori Ikari, Osman Wael Mohammed, Koichi Matsuda, Chikashi Terao, Koichiro Ohmura, Keiko Myouzen, Naoya Hosono, Tatsuhiko Tsunoda, Norihiro Nishimoto, Tsuneyo Mimori, Fumihiko Matsuda, Yoshiya Tanaka, Takayuki Sumida, Hisashi Yamanaka, Yoshinari Takasaki, Takao Koike, Takahiko Horiuchi, Kenshi Hayashi, Michiaki Kubo, Naoyuki Kamatani, Ryo Yamada, Yusuke Nakamura, Kazuhiko Yamamoto

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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.

Original languageEnglish
Article numbere1002455
JournalPLoS Genetics
Volume8
Issue number1
DOIs
Publication statusPublished - 2012 Jan

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ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)

Cite this

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., ... Yamamoto, K. (2012). A genome-wide association study identified AFF1 as a susceptibility locus for systemic lupus eyrthematosus in Japanese. PLoS Genetics, 8(1), [e1002455]. https://doi.org/10.1371/journal.pgen.1002455