Contribution of germline and somatic mutations to risk of neuromyelitis optica spectrum disorder

Yata, Tomohiro; Sato, Go; Ogawa, Kotaro; Naito, Tatsuhiko; Sonehara, Kyuto; Saiki, Ryunosuke; Edahiro, Ryuya; Namba, Shinichi; Watanabe, Mitsuru; Shirai, Yuya; Yamamoto, Kenichi; NamKoong, Ho; Nakanishi, Tomoko; Yamamoto, Yuji; Hosokawa, Akiko; Yamamoto, Mamoru; Oguro-Igashira, Eri

doi:https://doi.org/10.1016/j.xgen.2025.100776

Contribution of germline and somatic mutations to risk of neuromyelitis optica spectrum disorder

Yata, Tomohiro; Sato, Go; Ogawa, Kotaro et al.

Cell Genomics, 2025, 5(3), 100776

Number of Access:1,798（2025-08-14 04:12 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/100999

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Title	Contribution of germline and somatic mutations to risk of neuromyelitis optica spectrum disorder
Creator	CreatorName Yata, Tomohiro
	CreatorName Sato, Go
	NRID 1000080870500 1000080870500 researchmap permalink jihdiegisojosugudc jihdiegisojosugudc Scopus Author ID 57200553653 57200553653 CreatorName Ogawa, Kotaro
	CreatorName Naito, Tatsuhiko
	NRID 1000060975358 1000060975358 CreatorName Sonehara, Kyuto
	NRID 1000020982515 1000020982515 CreatorName Saiki, Ryunosuke
	researchmap permalink ryuya_edahiro_88 ryuya_edahiro_88 CreatorName Edahiro, Ryuya
	CreatorName Namba, Shinichi
	NRID 1000030748009 1000030748009 CreatorName Watanabe, Mitsuru
	NRID 1000050899945 1000050899945 CreatorName Shirai, Yuya
	NRID 1000090875585 1000090875585 ORCID 0000-0001-9594-7050 0000-0001-9594-7050 researchmap permalink KenichiYamamotoPed KenichiYamamotoPed Scopus Author ID 57204724143 57204724143 CreatorName Yamamoto, Kenichi
	NRID 1000050594644 1000050594644 CreatorName NamKoong, Ho
	NRID 1000070975359 1000070975359 CreatorName Nakanishi, Tomoko
	CreatorName Yamamoto, Yuji
	CreatorName Hosokawa, Akiko
	CreatorName Yamamoto, Mamoru
	NRID 1000051004139 1000051004139 researchmap permalink 51004139 51004139 CreatorName Oguro-Igashira, Eri
Subject	clonal hematopoiesis
	eQTL
	genome-wide association study
	human leukocyte antigen
	mosaic chromosomal alterations
	neuromyelitis optica spectrum disorder
	scRNA-seq
	single-cell RNA sequencing
	somatic mutation
Description	All authors are listed on pp1-2 of the article.
Description	Yata T., Sato G., Ogawa K., et al. Contribution of germline and somatic mutations to risk of neuromyelitis optica spectrum disorder. Cell Genomics 5, 100776 (2025); https://doi.org/10.1016/j.xgen.2025.100776.
Abstract	Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disease characterized by optic neuritis and transverse myelitis, with an unclear genetic background. A genome-wide meta-analysis of NMOSD in Japanese individuals (240 patients and 50,578 controls) identified significant associations with the major histocompatibility complex region and a common variant close to CCR6 (rs12193698; p = 1.8 × 10−8, odds ratio [OR] = 1.73). In single-cell RNA sequencing (scRNA-seq) analysis (25 patients and 101 controls), the CCR6 risk variant showed disease-specific expression quantitative trait loci effects in CD4+ T (CD4T) cell subsets. Furthermore, we detected somatic mosaic chromosomal alterations (mCAs) in various autoimmune diseases and found that mCAs increase the risk of NMOSD (OR = 3.37 for copy number alteration). In scRNA-seq data, CD4T cells with 21q loss, a recurrently observed somatic event in NMOSD, showed dysregulation of type I interferon-related genes. Our integrated study identified novel germline and somatic mutations associated with NMOSD pathogenesis.
Publisher	Cell Press
Source Title	Cell Genomics
Volume (Issue)	5(3)
Page	100776
Date of Issued	2025-03-12
Language	English
Handle URL	https://hdl.handle.net/11094/100999
eISSN	2666979X
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1016/j.xgen.2025.100776
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCTERMS.bibliographicCitation	Cell Genomics. 2025, 5(3), p. 100776
DC.title	Contribution of germline and somatic mutations to risk of neuromyelitis optica spectrum disorder
DC.creator	Yata, Tomohiro
	Sato, Go
	Ogawa, Kotaro
	Naito, Tatsuhiko
	Sonehara, Kyuto
	Saiki, Ryunosuke
	Edahiro, Ryuya
	Namba, Shinichi
	Watanabe, Mitsuru
	Shirai, Yuya
	Yamamoto, Kenichi
	NamKoong, Ho
	Nakanishi, Tomoko
	Yamamoto, Yuji
	Hosokawa, Akiko
	Yamamoto, Mamoru
	Oguro-Igashira, Eri
DC.publisher	Cell Press
DC.language' scheme='DCTERMS.RFC1766	English
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2025-03-12
DC.identifier	https://doi.org/10.1016/j.xgen.2025.100776
DC.subject	clonal hematopoiesis
	eQTL
	genome-wide association study
	human leukocyte antigen
	mosaic chromosomal alterations
	neuromyelitis optica spectrum disorder
	scRNA-seq
	single-cell RNA sequencing
	somatic mutation
DC.description	All authors are listed on pp1-2 of the article.
DC.description	Yata T., Sato G., Ogawa K., et al. Contribution of germline and somatic mutations to risk of neuromyelitis optica spectrum disorder. Cell Genomics 5, 100776 (2025); https://doi.org/10.1016/j.xgen.2025.100776.
DCTERMS.abstract	Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disease characterized by optic neuritis and transverse myelitis, with an unclear genetic background. A genome-wide meta-analysis of NMOSD in Japanese individuals (240 patients and 50,578 controls) identified significant associations with the major histocompatibility complex region and a common variant close to CCR6 (rs12193698; p = 1.8 × 10−8, odds ratio [OR] = 1.73). In single-cell RNA sequencing (scRNA-seq) analysis (25 patients and 101 controls), the CCR6 risk variant showed disease-specific expression quantitative trait loci effects in CD4+ T (CD4T) cell subsets. Furthermore, we detected somatic mosaic chromosomal alterations (mCAs) in various autoimmune diseases and found that mCAs increase the risk of NMOSD (OR = 3.37 for copy number alteration). In scRNA-seq data, CD4T cells with 21q loss, a recurrently observed somatic event in NMOSD, showed dysregulation of type I interferon-related genes. Our integrated study identified novel germline and somatic mutations associated with NMOSD pathogenesis.
DC.rights	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
DC.format	100999
citation_title	Contribution of germline and somatic mutations to risk of neuromyelitis optica spectrum disorder
citation_author	Yata, Tomohiro
	Sato, Go
	Ogawa, Kotaro
	Naito, Tatsuhiko
	Sonehara, Kyuto
	Saiki, Ryunosuke
	Edahiro, Ryuya
	Namba, Shinichi
	Watanabe, Mitsuru
	Shirai, Yuya
	Yamamoto, Kenichi
	NamKoong, Ho
	Nakanishi, Tomoko
	Yamamoto, Yuji
	Hosokawa, Akiko
	Yamamoto, Mamoru
	Oguro-Igashira, Eri
citation_publisher	Cell Press
citation_language	English
citation_date	2025-03-12
citation_journal_title	Cell Genomics
citation_volume	5
citation_issue	3
citation_firstpage	100776
citation_doi	https://doi.org/10.1016/j.xgen.2025.100776
citation_public_url	https://hdl.handle.net/11094/100999

Contribution of germline and somatic mutations to risk of neuromyelitis optica spectrum disorder

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