Author(s):
González-Muñoz, Sara ; Long, Yichen ; Guzmán-Jiménez, Andrea ; Cerván-Martín, Miriam ; Higueras-Serrano, Inmaculada ; CASTILLA, JOSE ANTONIO ; Clavero, Ana ; Garrido, Nicolas ; Luján, Saturnino ; Yang, Xiaoyu ; Guo, Xuejiang ; Liu, Jiayin ; Bassas, Lluís ; Seixas, Susana ; Gonçalves, João ; Lopes, Alexandra M. ; Larriba, Sara ; Bossini-Castillo, Lara ; Palomino-Morales, Rogelio J. ; Wang, Cheng ; HU, Zhibin ; Carmona, F. David
Date: 2025
Persistent ID: http://hdl.handle.net/10362/183513
Origin: Repositório Institucional da UNL
Subject(s): Medicine (miscellaneous); Biochemistry, Genetics and Molecular Biology(all); Agricultural and Biological Sciences(all)
Description
Funding Information: 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 \u201CInstituto de Salud Carlos III\u201D (grant: DTS18/00101], co-funded by FEDER funds/European Regional Development Fund (ERDF)- a way to build Europe-), and from \u201CGeneralitat de Catalunya\u201D (grant 2021SGR052). S. La is sponsored by the \u201CResearchers Consolidation Program\u201D from the SNS-Dpt. Salut Generalitat de Catalunya (Exp. CES09/020). The authors thank the support of the Unit of Excellence \u2018UNETE\u2019 from the University of Granada (reference UCE-PP2017-05). This article is related to the PhD Doctoral Thesis of Sara Gonz\u00E1lez-Mu\u00F1oz. Publisher Copyright: © The Author(s) 2025.
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.
