Trans-ethnic GWAS meta-analysis of idiopathic spermatogenic failure highlights the immune-mediated nature of Sertoli cell-only syndrome

Non-obstructive azoospermia, a severe form of male infertility caused by spermatogenic failure (SPGF), has a largely unknown genetic basis across ancestries. To our knowledge, this is the first trans-ethnic meta-analysis of genome-wide association studies on SPGF, involving 2255 men with idiopathic...

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Autores: González-Muñoz, Sara, Long, Yichen, Guzmán-Jimenez, Andrea, Cerván-Martín, Miriam, Higueras-Serrano, Inmaculada, Castilla, José A., Clavero, Ana, Garrido, Nicolás, Luján, Saturnino, Yang, Xiaoyu, Guo, Xuejiang, Liu, Jiayin, Bassas, Lluis, Seixas, Susana, Gonçalves, João, Lopes, Alexandra M., Larriba, Sara, Bossini-Castillo, Lara, Palomino-Morales, Rogelio, Wang, Cheng, Hu, Zhibin, Carmona, Francisco David
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/391492
Acceso en línea:http://hdl.handle.net/10261/391492
https://api.elsevier.com/content/abstract/scopus_id/105002984277
Access Level:acceso abierto
Palabra clave:Genome-wide association studies
Infertility
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oai_identifier_str oai:digital.csic.es:10261/391492
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Trans-ethnic GWAS meta-analysis of idiopathic spermatogenic failure highlights the immune-mediated nature of Sertoli cell-only syndrome
title Trans-ethnic GWAS meta-analysis of idiopathic spermatogenic failure highlights the immune-mediated nature of Sertoli cell-only syndrome
spellingShingle Trans-ethnic GWAS meta-analysis of idiopathic spermatogenic failure highlights the immune-mediated nature of Sertoli cell-only syndrome
González-Muñoz, Sara
Genome-wide association studies
Infertility
title_short Trans-ethnic GWAS meta-analysis of idiopathic spermatogenic failure highlights the immune-mediated nature of Sertoli cell-only syndrome
title_full Trans-ethnic GWAS meta-analysis of idiopathic spermatogenic failure highlights the immune-mediated nature of Sertoli cell-only syndrome
title_fullStr Trans-ethnic GWAS meta-analysis of idiopathic spermatogenic failure highlights the immune-mediated nature of Sertoli cell-only syndrome
title_full_unstemmed Trans-ethnic GWAS meta-analysis of idiopathic spermatogenic failure highlights the immune-mediated nature of Sertoli cell-only syndrome
title_sort Trans-ethnic GWAS meta-analysis of idiopathic spermatogenic failure highlights the immune-mediated nature of Sertoli cell-only syndrome
dc.creator.none.fl_str_mv González-Muñoz, Sara
Long, Yichen
Guzmán-Jimenez, Andrea
Cerván-Martín, Miriam
Higueras-Serrano, Inmaculada
Castilla, José A.
Clavero, Ana
Garrido, Nicolás
Luján, Saturnino
Yang, Xiaoyu
Guo, Xuejiang
Liu, Jiayin
Bassas, Lluis
Seixas, Susana
Gonçalves, João
Lopes, Alexandra M.
Larriba, Sara
Bossini-Castillo, Lara
Palomino-Morales, Rogelio
Wang, Cheng
Hu, Zhibin
Carmona, Francisco David
author González-Muñoz, Sara
author_facet González-Muñoz, Sara
Long, Yichen
Guzmán-Jimenez, Andrea
Cerván-Martín, Miriam
Higueras-Serrano, Inmaculada
Castilla, José A.
Clavero, Ana
Garrido, Nicolás
Luján, Saturnino
Yang, Xiaoyu
Guo, Xuejiang
Liu, Jiayin
Bassas, Lluis
Seixas, Susana
Gonçalves, João
Lopes, Alexandra M.
Larriba, Sara
Bossini-Castillo, Lara
Palomino-Morales, Rogelio
Wang, Cheng
Hu, Zhibin
Carmona, Francisco David
author_role author
author2 Long, Yichen
Guzmán-Jimenez, Andrea
Cerván-Martín, Miriam
Higueras-Serrano, Inmaculada
Castilla, José A.
Clavero, Ana
Garrido, Nicolás
Luján, Saturnino
Yang, Xiaoyu
Guo, Xuejiang
Liu, Jiayin
Bassas, Lluis
Seixas, Susana
Gonçalves, João
Lopes, Alexandra M.
Larriba, Sara
Bossini-Castillo, Lara
Palomino-Morales, Rogelio
Wang, Cheng
Hu, Zhibin
Carmona, Francisco David
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
Agencia Estatal de Investigación (España)
Ministerio de Ciencia, Innovación y Universidades (España)
National Key Research and Development Program (China)
Instituto de Salud Carlos III
European Commission
Generalitat de Catalunya
Universidad de Granada
González-Muñoz, Sara [0000-0001-7519-8320]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Genome-wide association studies
Infertility
topic Genome-wide association studies
Infertility
description Non-obstructive azoospermia, a severe form of male infertility caused by spermatogenic failure (SPGF), has a largely unknown genetic basis across ancestries. To our knowledge, this is the first trans-ethnic meta-analysis of genome-wide association studies on SPGF, involving 2255 men with idiopathic SPGF and 3608 controls from European and Asian populations. Using logistic regression and inverse variance methods, we identify two significant genetic associations with Sertoli cell-only (SCO) syndrome, the most extreme SPGF phenotype. The G allele of rs34915133, in the major histocompatibility complex class II region, significantly increases SCO risk (P = 5.25E-10, OR = 1.57), supporting a potential immune-related cause. Additionally, the rs10842262 variant in the SOX5 gene region is also a genetic marker of SCO (P = 5.29E-09, OR = 0.72), highlighting the key role of this gene in the male reproductive function. Our findings reveal shared genetic factors in male infertility across ancestries and provide insights into the molecular mechanisms underlying SCO.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/391492
https://api.elsevier.com/content/abstract/scopus_id/105002984277
url http://hdl.handle.net/10261/391492
https://api.elsevier.com/content/abstract/scopus_id/105002984277
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
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info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2023-152215OB-I00
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-120157RB-I00
info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016 (ISCIII)/DTS18%2F00101
González-Muñoz, Sara; Long, Yichen; Guzmán-Jimenez, Andrea; Cerván-Martín, Miriam; Higueras-Serrano, Inmaculada; Castilla, José A.; Clavero, Ana; Garrido, Nicolás; Luján, Saturnino; Yang, Xiaoyu; Guo, Xuejiang; Liu, Jiayin; Bassas, Lluis; Seixas, Susana; Gonçalves, João; Lopes, Alexandra M.; Larriba, Sara; Bossini-Castillo, Lara; Palomino-Morales, Rogelio J.; Wang, Cheng; Hu, Zhibin; Carmona, Francisco David; 2025; Supplementary Figures and Tables: Trans-ethnic GWAS meta-analysis of idiopathic spermatogenic failure highlights the immunemediated nature of Sertoli cell-only syndrome; Springer Nature; https://doi.org/10.1038/s42003-025-08001-2
https://doi.org/10.1038/s42003-025-08001-2
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
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dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Springer Nature
publisher.none.fl_str_mv Springer Nature
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
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spelling Trans-ethnic GWAS meta-analysis of idiopathic spermatogenic failure highlights the immune-mediated nature of Sertoli cell-only syndromeGonzález-Muñoz, SaraLong, YichenGuzmán-Jimenez, AndreaCerván-Martín, MiriamHigueras-Serrano, InmaculadaCastilla, José A.Clavero, AnaGarrido, NicolásLuján, SaturninoYang, XiaoyuGuo, XuejiangLiu, JiayinBassas, LluisSeixas, SusanaGonçalves, JoãoLopes, Alexandra M.Larriba, SaraBossini-Castillo, LaraPalomino-Morales, RogelioWang, ChengHu, ZhibinCarmona, Francisco DavidGenome-wide association studiesInfertilityNon-obstructive azoospermia, a severe form of male infertility caused by spermatogenic failure (SPGF), has a largely unknown genetic basis across ancestries. To our knowledge, this is the first trans-ethnic meta-analysis of genome-wide association studies on SPGF, involving 2255 men with idiopathic SPGF and 3608 controls from European and Asian populations. Using logistic regression and inverse variance methods, we identify two significant genetic associations with Sertoli cell-only (SCO) syndrome, the most extreme SPGF phenotype. The G allele of rs34915133, in the major histocompatibility complex class II region, significantly increases SCO risk (P = 5.25E-10, OR = 1.57), supporting a potential immune-related cause. Additionally, the rs10842262 variant in the SOX5 gene region is also a genetic marker of SCO (P = 5.29E-09, OR = 0.72), highlighting the key role of this gene in the male reproductive function. Our findings reveal shared genetic factors in male infertility across ancestries and provide insights into the molecular mechanisms underlying SCO.This work was supported by the Spanish Ministry of Economy and Competitiveness through the Spanish National Plan for Scientific and Technical Research and Innovation (grant: PID2023-152215OB-I00 funded by MICIU/AEI/10.13039/501100011033 and ERDF, EU; and grant: PID2020-120157RB-I00 funded by MICIU/AEI/10.13039/501100011033) and the National Key Research and Development Program of China (ref. 2021YFC2700201 and 2021YFC2700601). S.G.-M. was funded by grant ref. FPU23/02674. S. La received support from “Instituto de Salud Carlos III” (grant: DTS18/00101], co-funded by FEDER funds/European Regional Development Fund (ERDF)- a way to build Europe-), and from “Generalitat de Catalunya” (grant 2021SGR052). S. La is sponsored by the “Researchers Consolidation Program” from the SNS-Dpt. Salut Generalitat de Catalunya (Exp. CES09/020). The authors thank the support of the Unit of Excellence ‘UNETE’ from the University of Granada (reference UCE-PP2017-05). This article is related to the PhD Doctoral Thesis of Sara González-Muñoz.Peer reviewedSpringer NatureMinisterio de Economía y Competitividad (España)Agencia Estatal de Investigación (España)Ministerio de Ciencia, Innovación y Universidades (España)National Key Research and Development Program (China)Instituto de Salud Carlos IIIEuropean CommissionGeneralitat de CatalunyaUniversidad de GranadaGonzález-Muñoz, Sara [0000-0001-7519-8320]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202520252025info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/391492https://api.elsevier.com/content/abstract/scopus_id/105002984277reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2023-152215OB-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-120157RB-I00info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016 (ISCIII)/DTS18%2F00101González-Muñoz, Sara; Long, Yichen; Guzmán-Jimenez, Andrea; Cerván-Martín, Miriam; Higueras-Serrano, Inmaculada; Castilla, José A.; Clavero, Ana; Garrido, Nicolás; Luján, Saturnino; Yang, Xiaoyu; Guo, Xuejiang; Liu, Jiayin; Bassas, Lluis; Seixas, Susana; Gonçalves, João; Lopes, Alexandra M.; Larriba, Sara; Bossini-Castillo, Lara; Palomino-Morales, Rogelio J.; Wang, Cheng; Hu, Zhibin; Carmona, Francisco David; 2025; Supplementary Figures and Tables: Trans-ethnic GWAS meta-analysis of idiopathic spermatogenic failure highlights the immunemediated nature of Sertoli cell-only syndrome; Springer Nature; https://doi.org/10.1038/s42003-025-08001-2https://doi.org/10.1038/s42003-025-08001-2Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3914922026-05-22T06:33:51Z
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