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

Number of Access:41（2025-05-03 14:36 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/97842

Link to primary information

File	Format	Terms of use	Size	Views	Date.Available	Description	information
NatCommun_15_1_5744	pdf	None	1.10 MB	45	2024.09.10

Creative Commons : Attribution

Item Information

Output File Export EndNote Basic Export Mendeley

Title	Common and rare genetic variants predisposing females to unexplained recurrent pregnancy loss
Creator	NRID 1000060975358 1000060975358 CreatorName Sonehara, Kyuto
	NRID 1000040961537 1000040961537 CreatorName Yano, Yoshitaka
	researchmap permalink tnaito0315 tnaito0315 CreatorName Naito, Tatsuhiko
	NRID 1000090591909 1000090591909 CreatorName Goto, Shinobu
	NRID 1000030812094 1000030812094 CreatorName Yoshihara, Hiroyuki
	NRID 1000030726146 1000030726146 CreatorName Otani, Takahiro
	CreatorName Ozawa, Fumiko
	NRID 1000040444989 1000040444989 CreatorName Kitaori, Tamao
	NRID 1000090401257 1000090401257 CreatorName Matsuda, Koichi
	CreatorName Nishiyama, Takashi
	NRID 1000070727411 1000070727411 ORCID 0000-0002-0311-8472 0000-0002-0311-8472 researchmap permalink yokada yokada Scopus Author ID 7005443464 7005443464 CreatorName Okada, Yukinori
	NRID 1000030264740 1000030264740 CreatorName Sugiura-Ogasawara, Mayumi
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.
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.
Publisher	Nature Research
Source Title	Nature communications
Volume (Issue)	15(1)
Page	5744
Date of Issued	2024-07-17
Language	English
Handle URL	https://hdl.handle.net/11094/97842
eISSN	20411723
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1038/s41467-024-49993-5
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution 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	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	English
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	English
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

Link to primary information

Item Information

Show details