Common and rare genetic variants predisposing females to unexplained recurrent pregnancy loss

Sonehara, Kyuto; Yano, Yoshitaka; Naito, Tatsuhiko; Goto, Shinobu; Yoshihara, Hiroyuki; Otani, Takahiro; Ozawa, Fumiko; Kitaori, Tamao; Matsuda, Koichi; Nishiyama, Takashi; Okada, Yukinori; Sugiura-Ogasawara, Mayumi

doi:https://doi.org/10.1038/s41467-024-49993-5

Common and rare genetic variants predisposing females to unexplained recurrent pregnancy loss

Sonehara, Kyuto; Yano, Yoshitaka; Naito, Tatsuhiko et al.

Nature communications, 2024, 15(1), 5744

アクセス数:40件（2025-05-03 11:48 集計）

固定URL: https://hdl.handle.net/11094/97842

閲覧可能ファイル

ファイル	フォーマット	利用条件	サイズ	閲覧回数	利用開始日	説明	information
NatCommun_15_1_5744	pdf	なし	1.10 MB	45	2024.09.10

Creative Commons : 表示

論文情報

ファイル出力 EndNote Basic出力 Mendeley出力

タイトル	Common and rare genetic variants predisposing females to unexplained recurrent pregnancy loss
著者	NRID 1000060975358 1000060975358 著者名 Sonehara, Kyuto
	NRID 1000040961537 1000040961537 著者名 Yano, Yoshitaka
	researchmap permalink tnaito0315 tnaito0315 著者名 Naito, Tatsuhiko
	NRID 1000090591909 1000090591909 著者名 Goto, Shinobu
	NRID 1000030812094 1000030812094 著者名 Yoshihara, Hiroyuki
	NRID 1000030726146 1000030726146 著者名 Otani, Takahiro
	著者名 Ozawa, Fumiko
	NRID 1000040444989 1000040444989 著者名 Kitaori, Tamao
	NRID 1000090401257 1000090401257 著者名 Matsuda, Koichi
	著者名 Nishiyama, Takashi
	NRID 1000070727411 1000070727411 ORCID 0000-0002-0311-8472 0000-0002-0311-8472 researchmap permalink yokada yokada Scopus Author ID 7005443464 7005443464 著者名 Okada, Yukinori
	NRID 1000030264740 1000030264740 著者名 Sugiura-Ogasawara, Mayumi
内容	Sonehara K., Yano Y., Naito T., et al. Common and rare genetic variants predisposing females to unexplained recurrent pregnancy loss. Nature communications 15, 5744 (2024); https://doi.org/10.1038/s41467-024-49993-5.
抄録	Recurrent pregnancy loss (RPL) is a major reproductive health issue with multifactorial causes, affecting 2.6% of all pregnancies worldwide. Nearly half of the RPL cases lack clinically identifiable causes (e.g., antiphospholipid syndrome, uterine anomalies, and parental chromosomal abnormalities), referred to as unexplained RPL (uRPL). Here, we perform a genome-wide association study focusing on uRPL in 1,728 cases and 24,315 female controls of Japanese ancestry. We detect significant associations in the major histocompatibility complex (MHC) region at 6p21 (lead variant=rs9263738; P = 1.4 × 10-10; odds ratio [OR] = 1.51 [95% CI: 1.33-1.72]; risk allele frequency = 0.871). The MHC associations are fine-mapped to the classical HLA alleles, HLA-C12:02, HLA-B52:01, and HLA-DRB1*15:02 (P = 1.1 × 10-10, 1.5 × 10-10, and 1.2 × 10-9, respectively), which constitute a population-specific common long-range haplotype with a protective effect (P = 2.8 × 10-10; OR = 0.65 [95% CI: 0.57-0.75]; haplotype frequency=0.108). Genome-wide copy-number variation (CNV) calling demonstrates rare predicted loss-of-function (pLoF) variants of the cadherin-11 gene (CDH11) conferring the risk of uRPL (P = 1.3 × 10-4; OR = 3.29 [95% CI: 1.78-5.76]). Our study highlights the importance of reproductive immunology and rare variants in the uRPL etiology.
出版者	Nature Research
収録物名	Nature communications
巻(号)	15(1)
ページ	5744
刊行年月	2024-07-17
言語	英語
ハンドルURL	https://hdl.handle.net/11094/97842
eISSN	20411723
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1038/s41467-024-49993-5
アクセス権	open access
権利情報	This article is licensed under a Creative Commons Attribution 4.0 International License.
出版タイプ	Version of Record
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCTERMS.bibliographicCitation	Nature communications. 2024, 15(1), p. 5744
DC.title	Common and rare genetic variants predisposing females to unexplained recurrent pregnancy loss
DC.creator	Sonehara, Kyuto
	Yano, Yoshitaka
	Naito, Tatsuhiko
	Goto, Shinobu
	Yoshihara, Hiroyuki
	Otani, Takahiro
	Ozawa, Fumiko
	Kitaori, Tamao
	Matsuda, Koichi
	Nishiyama, Takashi
	Okada, Yukinori
	Sugiura-Ogasawara, Mayumi
DC.publisher	Nature Research
DC.language' scheme='DCTERMS.RFC1766	英語
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2024-07-17
DC.identifier	https://doi.org/10.1038/s41467-024-49993-5
DC.description	Sonehara K., Yano Y., Naito T., et al. Common and rare genetic variants predisposing females to unexplained recurrent pregnancy loss. Nature communications 15, 5744 (2024); https://doi.org/10.1038/s41467-024-49993-5.
DCTERMS.abstract	Recurrent pregnancy loss (RPL) is a major reproductive health issue with multifactorial causes, affecting 2.6% of all pregnancies worldwide. Nearly half of the RPL cases lack clinically identifiable causes (e.g., antiphospholipid syndrome, uterine anomalies, and parental chromosomal abnormalities), referred to as unexplained RPL (uRPL). Here, we perform a genome-wide association study focusing on uRPL in 1,728 cases and 24,315 female controls of Japanese ancestry. We detect significant associations in the major histocompatibility complex (MHC) region at 6p21 (lead variant=rs9263738; P = 1.4 × 10-10; odds ratio [OR] = 1.51 [95% CI: 1.33-1.72]; risk allele frequency = 0.871). The MHC associations are fine-mapped to the classical HLA alleles, HLA-C12:02, HLA-B52:01, and HLA-DRB1*15:02 (P = 1.1 × 10-10, 1.5 × 10-10, and 1.2 × 10-9, respectively), which constitute a population-specific common long-range haplotype with a protective effect (P = 2.8 × 10-10; OR = 0.65 [95% CI: 0.57-0.75]; haplotype frequency=0.108). Genome-wide copy-number variation (CNV) calling demonstrates rare predicted loss-of-function (pLoF) variants of the cadherin-11 gene (CDH11) conferring the risk of uRPL (P = 1.3 × 10-4; OR = 3.29 [95% CI: 1.78-5.76]). Our study highlights the importance of reproductive immunology and rare variants in the uRPL etiology.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	97842
citation_title	Common and rare genetic variants predisposing females to unexplained recurrent pregnancy loss
citation_author	Sonehara, Kyuto
	Yano, Yoshitaka
	Naito, Tatsuhiko
	Goto, Shinobu
	Yoshihara, Hiroyuki
	Otani, Takahiro
	Ozawa, Fumiko
	Kitaori, Tamao
	Matsuda, Koichi
	Nishiyama, Takashi
	Okada, Yukinori
	Sugiura-Ogasawara, Mayumi
citation_publisher	Nature Research
citation_language	英語
citation_date	2024-07-17
citation_journal_title	Nature communications
citation_volume	15
citation_issue	1
citation_firstpage	5744
citation_doi	https://doi.org/10.1038/s41467-024-49993-5
citation_public_url	https://hdl.handle.net/11094/97842

Common and rare genetic variants predisposing females to unexplained recurrent pregnancy loss

閲覧可能ファイル

論文情報

論文詳細を表示