2025-08-29 東京大学,大阪大学,理化学研究所,東京科学大学,名古屋市立大学
日本人を対象とした乾癬の全ゲノム配列解析
<関連情報>
- https://www.u-tokyo.ac.jp/content/400269615.pdf
- https://www.cell.com/cell-genomics/fulltext/S2666-979X(25)00234-4
全ゲノムシーケンシングにより乾癬に寄与する稀な構造変異を解明し、リスク遺伝子としてCERCAMを同定 Whole-genome sequencing reveals rare and structural variants contributing to psoriasis and identifies CERCAM as a risk gene
Kyuto Sonehara ∙ Rei Watanabe ∙ Yutaka Matsumura ∙ … ∙ Manabu Fujimoto ∙ Akimichi Morita ∙ Yukinori Okada
Cell Genomics Published:August 22, 2025
DOI:https://doi.org/10.1016/j.xgen.2025.100978
Highlights
- Whole-genome sequencing study of 5,383 Japanese individuals for psoriasis genetics
- Structural variant analysis reveals a likely causal 3.3-kb deletion at IFNLR1 enhancer
- Gene-based rare-variant analysis identifies CERCAM as a psoriasis susceptibility gene
- Cercam knockout in a psoriasis mouse model demonstrated aggravated dermatitis
Summary
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.
