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

Kyuto Sonehara, Yoshitaka Yano, Tatsuhiko Naito, Shinobu Goto, Hiroyuki Yoshihara, Takahiro Otani, Fumiko Ozawa, Tamao Kitaori, Koichi Matsuda, Takashi Nishiyama, Yukinori Okada () and Mayumi Sugiura-Ogasawara ()
Additional contact information
Kyuto Sonehara: the University of Tokyo
Yoshitaka Yano: Nagoya City University Graduate School of Medical Sciences
Tatsuhiko Naito: Osaka University Graduate School of Medicine
Shinobu Goto: Nagoya City University Graduate School of Medical Sciences
Hiroyuki Yoshihara: Nagoya City University Graduate School of Medical Sciences
Takahiro Otani: Nagoya City University Graduate School of Medical Sciences
Fumiko Ozawa: Nagoya City University Graduate School of Medical Sciences
Tamao Kitaori: Nagoya City University Graduate School of Medical Sciences
Koichi Matsuda: The University of Tokyo
Takashi Nishiyama: Nagoya City University Graduate School of Medical Sciences
Yukinori Okada: the University of Tokyo
Mayumi Sugiura-Ogasawara: Nagoya City University Graduate School of Medical Sciences

Nature Communications, 2024, vol. 15, issue 1, 1-9

Abstract: 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-C*12:02, HLA-B*52:01, 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.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-49993-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49993-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-49993-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().