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; 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

doi:10.1371/journal.pgen.1002455

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 language	English
Article number	e1002455
Journal	PLoS Genetics
Volume	8
Issue number	1
DOIs	https://doi.org/10.1371/journal.pgen.1002455
Publication status	Published - 01-2012
Externally published	Yes

All Science Journal Classification (ASJC) codes

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1371/journal.pgen.1002455

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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), Article e1002455. https://doi.org/10.1371/journal.pgen.1002455

@article{d4707fc05d504408bfeaaca52dcc7815,

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.",

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

year = "2012",

month = jan,

doi = "10.1371/journal.pgen.1002455",

language = "English",

volume = "8",

journal = "PLoS Genetics",

issn = "1553-7390",

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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

TY - JOUR

T1 - A genome-wide association study identified AFF1 as a susceptibility locus for systemic lupus eyrthematosus in Japanese

AU - Okada, Yukinori

AU - Shimane, Kenichi

AU - Kochi, Yuta

AU - Tahira, Tomoko

AU - Suzuki, Akari

AU - Higasa, Koichiro

AU - Takahashi, Atsushi

AU - Horita, Tetsuya

AU - Atsumi, Tatsuya

AU - Ishii, Tomonori

AU - Okamoto, Akiko

AU - Fujio, Keishi

AU - Hirakata, Michito

AU - Amano, Hirofumi

AU - Kondo, Yuya

AU - Ito, Satoshi

AU - Takada, Kazuki

AU - Mimori, Akio

AU - Saito, Kazuyoshi

AU - Kamachi, Makoto

AU - Kawaguchi, Yasushi

AU - Ikari, Katsunori

AU - Mohammed, Osman Wael

AU - Matsuda, Koichi

AU - Terao, Chikashi

AU - Ohmura, Koichiro

AU - Myouzen, Keiko

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

AU - Kamatani, Naoyuki

AU - Yamada, Ryo

AU - Nakamura, Yusuke

AU - Yamamoto, Kazuhiko

PY - 2012/1

Y1 - 2012/1

N2 - 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.

AB - 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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SN - 1553-7390

VL - 8

JO - PLoS Genetics

JF - PLoS Genetics

IS - 1

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ER -

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

Abstract

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