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 Kamachi & 24 others Yasushi 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

Research output: Contribution to journalArticle

74 Citations (Scopus)

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 - Jan 1 2012

Fingerprint

lupus erythematosus
Genome-Wide Association Study
Systemic Lupus Erythematosus
genome
Quantitative Trait Loci
loci
quantitative trait loci
autoimmune diseases
gene
Autoimmune Diseases
abnormality
lymphocytes
allele
Lymphocytes
blood
damage
genome-wide association study
family
odds ratio
Genes

All Science Journal Classification (ASJC) codes

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

Cite this

Okada, Y., Shimane, K., Kochi, Y., Tahira, T., Suzuki, A., Higasa, 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

A genome-wide association study identified AFF1 as a susceptibility locus for systemic lupus eyrthematosus in Japanese. / Okada, Yukinori; Shimane, Kenichi; Kochi, Yuta; Tahira, Tomoko; Suzuki, Akari; Higasa, Koichiro; Takahashi, Atsushi; Horita, Tetsuya; Atsumi, Tatsuya; Ishii, Tomonori; Okamoto, Akiko; Fujio, Keishi; Hirakata, Michito; Amano, Hirofumi; Kondo, Yuya; Ito, Satoshi; Takada, Kazuki; Mimori, Akio; Saito, Kazuyoshi; Kamachi, Makoto; Kawaguchi, Yasushi; Ikari, Katsunori; Mohammed, Osman Wael; Matsuda, Koichi; Terao, Chikashi; Ohmura, Koichiro; Myouzen, Keiko; Hosono, Naoya; Tsunoda, Tatsuhiko; Nishimoto, Norihiro; Mimori, Tsuneyo; Matsuda, Fumihiko; Tanaka, Yoshiya; Sumida, Takayuki; Yamanaka, Hisashi; Takasaki, Yoshinari; Koike, Takao; Horiuchi, Takahiko; Hayashi, Kenshi; Kubo, Michiaki; Kamatani, Naoyuki; Yamada, Ryo; Nakamura, Yusuke; Yamamoto, Kazuhiko.

In: PLoS genetics, Vol. 8, No. 1, e1002455, 01.01.2012.

Research output: Contribution to journalArticle

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 2012, 'A genome-wide association study identified AFF1 as a susceptibility locus for systemic lupus eyrthematosus in Japanese', PLoS genetics, vol. 8, no. 1, e1002455. https://doi.org/10.1371/journal.pgen.1002455
Okada, Yukinori ; Shimane, Kenichi ; Kochi, Yuta ; Tahira, Tomoko ; Suzuki, Akari ; Higasa, Koichiro ; Takahashi, Atsushi ; Horita, Tetsuya ; Atsumi, Tatsuya ; Ishii, Tomonori ; Okamoto, Akiko ; Fujio, Keishi ; Hirakata, Michito ; Amano, Hirofumi ; Kondo, Yuya ; Ito, Satoshi ; Takada, Kazuki ; Mimori, Akio ; Saito, Kazuyoshi ; Kamachi, Makoto ; Kawaguchi, Yasushi ; Ikari, Katsunori ; Mohammed, Osman Wael ; Matsuda, Koichi ; Terao, Chikashi ; Ohmura, Koichiro ; Myouzen, Keiko ; Hosono, Naoya ; Tsunoda, Tatsuhiko ; Nishimoto, Norihiro ; Mimori, Tsuneyo ; Matsuda, Fumihiko ; Tanaka, Yoshiya ; Sumida, Takayuki ; Yamanaka, Hisashi ; Takasaki, Yoshinari ; Koike, Takao ; Horiuchi, Takahiko ; Hayashi, Kenshi ; Kubo, Michiaki ; Kamatani, Naoyuki ; Yamada, Ryo ; Nakamura, Yusuke ; Yamamoto, Kazuhiko. / A genome-wide association study identified AFF1 as a susceptibility locus for systemic lupus eyrthematosus in Japanese. In: PLoS genetics. 2012 ; Vol. 8, No. 1.
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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.",
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AU - Tahira, Tomoko

AU - Suzuki, Akari

AU - Higasa, Koichiro

AU - Takahashi, Atsushi

AU - Horita, Tetsuya

AU - Atsumi, Tatsuya

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AU - Kamachi, Makoto

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AU - Ikari, Katsunori

AU - Mohammed, Osman Wael

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AU - Terao, Chikashi

AU - Ohmura, Koichiro

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AU - Hosono, Naoya

AU - Tsunoda, Tatsuhiko

AU - Nishimoto, Norihiro

AU - Mimori, Tsuneyo

AU - Matsuda, Fumihiko

AU - Tanaka, Yoshiya

AU - Sumida, Takayuki

AU - Yamanaka, Hisashi

AU - Takasaki, Yoshinari

AU - Koike, Takao

AU - Horiuchi, Takahiko

AU - Hayashi, Kenshi

AU - Kubo, Michiaki

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