Kyuto Sonehara, Rei Watanabe, Yutaka Matsumura, Yuichi Mitsui, Yosuke Ogawa, Kaori Odomari, Saori Sakaue, Shinichi Namba, Mariko Komuro, Mio Edamoto, Junya Watanabe, Tomomitsu Hirota, Noriko Arase, Yuumi Nakamura, Kimiko Nakajima, Takashi Okamoto, Rika Nishikawa, Kenichi Yamamoto, Ken Suzuki, Toshihiro Kishikawa, Ryuya Edahiro, Yuya Shirai, Tatsuhiko Naito, Noah Sasa, Yosuke Ishitsuka, Junichi Furuta, Kayo Kunimoto, Ikko Kajihara, Satoshi Fukushima, Hideaki Miyachi, Hiroyuki Matsue, Masahiro Kamata, Mami Momose, Ippei Miyagawa, Hiroaki Tanaka, Masanobu Ueno, Toshinori Bito, Hiroshi Nagai, Tetsuya Ikeda, Tatsuya Horikawa, Atsuko Adachi, Tsukasa Matsubara, Emi Nishida, Koichi Matsuda, Nobuhiro Shojima, Ikuma Nakagawa, Yoshihide Asano, Shinichi Sato, Shinichi Imafuku, Yayoi Tada, Chikako Nishigori, Masatoshi Jinnin, Hironobu Ihn, Akihiko Asahina, Hidehisa Saeki, Toshimasa Yamauchi, Takashi Kadowaki, Tatsuyoshi Kawamura, Shinji Shimada, Ichiro Katayama, Koichiro Higasa, Emiko Noguchi, Shigetoshi Sano, Yoshiya Tanaka, Fumihiko Matsuda, Atsushi Kumanogoh, Mayumi Tamari, Takashi Satoh, Manabu Fujimoto, Akimichi Morita, Yukinori Okada
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{"title":"全基因组测序揭示了导致牛皮癣的罕见和结构变异，并将CERCAM确定为风险基因。","authors":"Kyuto Sonehara, Rei Watanabe, Yutaka Matsumura, Yuichi Mitsui, Yosuke Ogawa, Kaori Odomari, Saori Sakaue, Shinichi Namba, Mariko Komuro, Mio Edamoto, Junya Watanabe, Tomomitsu Hirota, Noriko Arase, Yuumi Nakamura, Kimiko Nakajima, Takashi Okamoto, Rika Nishikawa, Kenichi Yamamoto, Ken Suzuki, Toshihiro Kishikawa, Ryuya Edahiro, Yuya Shirai, Tatsuhiko Naito, Noah Sasa, Yosuke Ishitsuka, Junichi Furuta, Kayo Kunimoto, Ikko Kajihara, Satoshi Fukushima, Hideaki Miyachi, Hiroyuki Matsue, Masahiro Kamata, Mami Momose, Ippei Miyagawa, Hiroaki Tanaka, Masanobu Ueno, Toshinori Bito, Hiroshi Nagai, Tetsuya Ikeda, Tatsuya Horikawa, Atsuko Adachi, Tsukasa Matsubara, Emi Nishida, Koichi Matsuda, Nobuhiro Shojima, Ikuma Nakagawa, Yoshihide Asano, Shinichi Sato, Shinichi Imafuku, Yayoi Tada, Chikako Nishigori, Masatoshi Jinnin, Hironobu Ihn, Akihiko Asahina, Hidehisa Saeki, Toshimasa Yamauchi, Takashi Kadowaki, Tatsuyoshi Kawamura, Shinji Shimada, Ichiro Katayama, Koichiro Higasa, Emiko Noguchi, Shigetoshi Sano, Yoshiya Tanaka, Fumihiko Matsuda, Atsushi Kumanogoh, Mayumi Tamari, Takashi Satoh, Manabu Fujimoto, Akimichi Morita, Yukinori Okada","doi":"10.1016/j.xgen.2025.100978","DOIUrl":null,"url":null,"abstract":"<p><p>Psoriasis vulgaris (PsV) is an immune-mediated inflammatory skin disorder with complex genetic architecture. Most genome-wide association studies (GWASs) of PsV have been limited to analyzing common single-nucleotide variants in Europeans, lacking diversity in the variant spectrum and ancestral background. To investigate the contribution of rare variants (RVs) and structural variants (SVs), we perform a whole-genome sequencing study involving 1,415 PsV cases and 3,968 controls in Japanese. A GWAS signal at IFNLR1 is fine-mapped to a 3.3-kb deletion SV disrupting an epithelium-specific putative enhancer, which is validated by PacBio long-read sequencing. Gene-based RV analyses identify two susceptibility genes: IFIH1 (p = 9.8 × 10<sup>-6</sup>) and CERCAM (p = 4.1 × 10<sup>-7</sup>). Notably, IL36RN, a causative gene for generalized pustular psoriasis, a rare and lethal multi-systemic inflammatory disorder, is associated with common PsV (p = 1.2 × 10<sup>-4</sup>). Finally, Cercam knockout (Cercam<sup>-/-</sup>) in an imiquimod-induced psoriasis mouse model aggravates dermatitis with elevated T cell retention in the subepidermis. Our study elucidates the overlooked genetic basis of PsV.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100978"},"PeriodicalIF":11.1000,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Whole-genome sequencing reveals rare and structural variants contributing to psoriasis and identifies CERCAM as a risk gene.\",\"authors\":\"Kyuto Sonehara, Rei Watanabe, Yutaka Matsumura, Yuichi Mitsui, Yosuke Ogawa, Kaori Odomari, Saori Sakaue, Shinichi Namba, Mariko Komuro, Mio Edamoto, Junya Watanabe, Tomomitsu Hirota, Noriko Arase, Yuumi Nakamura, Kimiko Nakajima, Takashi Okamoto, Rika Nishikawa, Kenichi Yamamoto, Ken Suzuki, Toshihiro Kishikawa, Ryuya Edahiro, Yuya Shirai, Tatsuhiko Naito, Noah Sasa, Yosuke Ishitsuka, Junichi Furuta, Kayo Kunimoto, Ikko Kajihara, Satoshi Fukushima, Hideaki Miyachi, Hiroyuki Matsue, Masahiro Kamata, Mami Momose, Ippei Miyagawa, Hiroaki Tanaka, Masanobu Ueno, Toshinori Bito, Hiroshi Nagai, Tetsuya Ikeda, Tatsuya Horikawa, Atsuko Adachi, Tsukasa Matsubara, Emi Nishida, Koichi Matsuda, Nobuhiro Shojima, Ikuma Nakagawa, Yoshihide Asano, Shinichi Sato, Shinichi Imafuku, Yayoi Tada, Chikako Nishigori, Masatoshi Jinnin, Hironobu Ihn, Akihiko Asahina, Hidehisa Saeki, Toshimasa Yamauchi, Takashi Kadowaki, Tatsuyoshi Kawamura, Shinji Shimada, Ichiro Katayama, Koichiro Higasa, Emiko Noguchi, Shigetoshi Sano, Yoshiya Tanaka, Fumihiko Matsuda, Atsushi Kumanogoh, Mayumi Tamari, Takashi Satoh, Manabu Fujimoto, Akimichi Morita, Yukinori Okada\",\"doi\":\"10.1016/j.xgen.2025.100978\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Psoriasis vulgaris (PsV) is an immune-mediated inflammatory skin disorder with complex genetic architecture. Most genome-wide association studies (GWASs) of PsV have been limited to analyzing common single-nucleotide variants in Europeans, lacking diversity in the variant spectrum and ancestral background. To investigate the contribution of rare variants (RVs) and structural variants (SVs), we perform a whole-genome sequencing study involving 1,415 PsV cases and 3,968 controls in Japanese. A GWAS signal at IFNLR1 is fine-mapped to a 3.3-kb deletion SV disrupting an epithelium-specific putative enhancer, which is validated by PacBio long-read sequencing. Gene-based RV analyses identify two susceptibility genes: IFIH1 (p = 9.8 × 10<sup>-6</sup>) and CERCAM (p = 4.1 × 10<sup>-7</sup>). Notably, IL36RN, a causative gene for generalized pustular psoriasis, a rare and lethal multi-systemic inflammatory disorder, is associated with common PsV (p = 1.2 × 10<sup>-4</sup>). Finally, Cercam knockout (Cercam<sup>-/-</sup>) in an imiquimod-induced psoriasis mouse model aggravates dermatitis with elevated T cell retention in the subepidermis. Our study elucidates the overlooked genetic basis of PsV.</p>\",\"PeriodicalId\":72539,\"journal\":{\"name\":\"Cell genomics\",\"volume\":\" \",\"pages\":\"100978\"},\"PeriodicalIF\":11.1000,\"publicationDate\":\"2025-08-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell genomics\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1016/j.xgen.2025.100978\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell genomics","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.xgen.2025.100978","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
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