Медицинская библиотека · Cell genomics · 2025

Whole-genome sequencing reveals rare and structural variants contributing to psoriasis and identifies CERCAM as a risk gene.

Sonehara Kyuto, Watanabe Rei, Matsumura Yutaka, Mitsui Yuichi, Ogawa Yosuke, Odomari Kaori, Sakaue Saori, Namba Shinichi, Komuro Mariko, Edamoto Mio, Watanabe Junya, Hirota Tomomitsu, Arase Noriko, Nakamura Yuumi, Nakajima Kimiko, Okamoto Takashi, Nishikawa Rika, Yamamoto Kenichi, Suzuki Ken, Kishikawa Toshihiro, Edahiro Ryuya, Shirai Yuya, Naito Tatsuhiko, Sasa Noah, Ishitsuka Yosuke, Furuta Junichi, Kunimoto Kayo, Kajihara Ikko, Fukushima Satoshi, Miyachi Hideaki, Matsue Hiroyuki, Kamata Masahiro, Momose Mami, Miyagawa Ippei, Tanaka Hiroaki, Ueno Masanobu, Bito Toshinori, Nagai Hiroshi, Ikeda Tetsuya, Horikawa Tatsuya, Adachi Atsuko, Matsubara Tsukasa, Nishida Emi, Biobank Japan Project, Matsuda Koichi, Shojima Nobuhiro, Nakagawa Ikuma, Asano Yoshihide, Sato Shinichi, Imafuku Shinichi, Tada Yayoi, Nishigori Chikako, Jinnin Masatoshi, Ihn Hironobu, Asahina Akihiko, Saeki Hidehisa, Yamauchi Toshimasa, Kadowaki Takashi, Kawamura Tatsuyoshi, Shimada Shinji, Katayama Ichiro, Higasa Koichiro, Noguchi Emiko, Sano Shigetoshi, Tanaka Yoshiya, Matsuda Fumihiko, Kumanogoh Atsushi, Tamari Mayumi, Satoh Takashi, Fujimoto Manabu, Morita Akimichi, Okada Yukinori

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Аннотация

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 × 10-6) and CERCAM (p = 4.1 × 10-7). 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 × 10-4). Finally, Cercam knockout (Cercam-/-) 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.

Для цитирования: Sonehara Kyuto, Watanabe Rei, Matsumura Yutaka, Mitsui Yuichi, Ogawa Yosuke, Odomari Kaori, Sakaue Saori, Namba Shinichi, Komuro Mariko, Edamoto Mio, Watanabe Junya, Hirota Tomomitsu, Arase Noriko, Nakamura Yuumi, Nakajima Kimiko, Okamoto Takashi, Nishikawa Rika, Yamamoto Kenichi, Suzuki Ken, Kishikawa Toshihiro, Edahiro Ryuya, Shirai Yuya, Naito Tatsuhiko, Sasa Noah, Ishitsuka Yosuke, Furuta Junichi, Kunimoto Kayo, Kajihara Ikko, Fukushima Satoshi, Miyachi Hideaki, Matsue Hiroyuki, Kamata Masahiro, Momose Mami, Miyagawa Ippei, Tanaka Hiroaki, Ueno Masanobu, Bito Toshinori, Nagai Hiroshi, Ikeda Tetsuya, Horikawa Tatsuya, Adachi Atsuko, Matsubara Tsukasa, Nishida Emi, Biobank Japan Project, Matsuda Koichi, Shojima Nobuhiro, Nakagawa Ikuma, Asano Yoshihide, Sato Shinichi, Imafuku Shinichi, Tada Yayoi, Nishigori Chikako, Jinnin Masatoshi, Ihn Hironobu, Asahina Akihiko, Saeki Hidehisa, Yamauchi Toshimasa, Kadowaki Takashi, Kawamura Tatsuyoshi, Shimada Shinji, Katayama Ichiro, Higasa Koichiro, Noguchi Emiko, Sano Shigetoshi, Tanaka Yoshiya, Matsuda Fumihiko, Kumanogoh Atsushi, Tamari Mayumi, Satoh Takashi, Fujimoto Manabu, Morita Akimichi, Okada Yukinori. Whole-genome sequencing reveals rare and structural variants contributing to psoriasis and identifies CERCAM as a risk gene.. Cell genomics. 2025. DOI: 10.1016/j.xgen.2025.100978.

Предметные рубрики MeSH

Psoriasis Humans Animals Genetic Predisposition to Disease Mice Genome-Wide Association Study Whole Genome Sequencing Polymorphism, Single Nucleotide Male Female Mice, Knockout Disease Models, Animal Interferon-Induced Helicase, IFIH1

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