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

被引：0

作者：

Gonzalez-Munoz, Sara ^{[1
,2
]}

Long, Yichen ^{[3
,4
]}

Guzman-Jimenez, Andrea ^{[1
,2
]}

Cervan-Martin, Miriam ^{[5
]}

Higueras-Serrano, Inmaculada ^{[1
]}

Castilla, Jose A. ^{[2
,6
]}

Clavero, Ana ^{[2
,7
]}

Garrido, Nicolas ^{[8
,9
,10
]}

Lujan, Saturnino ^{[9
,10
]}

Yang, Xiaoyu ^{[3
,11
]}

Guo, Xuejiang ^{[3
]}

Liu, Jiayin ^{[3
,11
]}

Bassas, Lluis ^{[12
]}

Seixas, Susana ^{[13
,14
]}

Goncalves, Joao ^{[15
,16
]}

Lopes, Alexandra M. ^{[13
,14
,17
]}

Larriba, Sara ^{[18
]}

Bossini-Castillo, Lara ^{[1
,2
]}

Palomino-Morales, Rogelio J. ^{[2
,19
]}

Wang, Cheng ^{[3
,4
]}

Hu, Zhibin ^{[3
,4
]}

Carmona, F. David ^{[1
,2
]}

机构：

[1] Univ Granada, Ctr Invest Biomed CIBM, Inst Biotecnol, Granada, Spain

[2] Inst Invest Biosanit ibs GRANADA, Granada, Spain

[3] Nanjing Med Univ, State Key Lab Reprod Med & Offspring Hlth, Nanjing, Peoples R China

[4] Nanjing Med Univ, Ctr Global Hlth, Sch Publ Hlth, Dept Epidemiol, Nanjing, Peoples R China

[5] CSIC, Inst Parasitol & Biomed Lopez Neyra IPBLN, Granada, Spain

[6] Univ Granada, Fac Med, Dept Anat & Embriol Humana, Granada, Spain

[7] HU Virgen Nieves, UGC Obstet & Ginecol, Unidad Reprod, Granada, Spain

[8] Hlth Inst Res La Fe, IVI Fdn, IVIRMA Global Res Alliance, Valencia, Spain

[9] Hosp Univ & Politecn La Fe, Serv Urol, Valencia, Spain

[10] Inst Invest Sanitaria La Fe IIS Fe, Valencia, Spain

[11] Nanjing Med Univ, Affiliated Hosp 1, Clin Ctr Reprod Med, Nanjing, Peoples R China

[12] Androl Serv Fundacio Puigvert, Lab Seminol & Embryol, Barcelona, Spain

[13] Univ Porto I3S, Inst Invest & Inovacao Saude, Porto, Portugal

[14] Univ Porto IPATIMUP, Inst Mol Pathol & Immunol, Porto, Portugal

[15] Inst Nacl Saude Dr Ricardo Jorge, Dept Genet Humana, Inst Nacl Saude Dr, Lisbon, Portugal

[16] Nova Med Sch, ToxOmics Ctr Toxicogen & Saude Humana, Lisbon, Portugal

[17] Univ Porto, Inst Cell & Mol Biol, Ctr Predict & Prevent Genet, Porto, Portugal

[18] Inst Invest Biomed Bellvitge IDIBELL, Genes Dis & Therapy Program, ImmuneInflammatory Proc & Gene Therapeut Grp, Barcelona, Spain

[19] Univ Granada, Dept Bioquim & Biol Mol 1, Granada, Spain

来源：

COMMUNICATIONS BIOLOGY | 2025年 / 8卷 / 01期

关键词：

BLOOD-TESTIS BARRIER; NONOBSTRUCTIVE AZOOSPERMIA; VARIANTS; REGION; ASSOCIATION; INFERTILITY; GUIDELINE; DIAGNOSIS; REVEALS; GENES;

D O I：

10.1038/s42003-025-08001-2

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：11

共 72 条

[1] The GTEx Consortium atlas of genetic regulatory effects across human tissues [J].

Aguet, Francois ;

Barbeira, Alvaro N. ;

Bonazzola, Rodrigo ;

Brown, Andrew ;

Castel, Stephane E. ;

Jo, Brian ;

Kasela, Silva ;

Kim-Hellmuth, Sarah ;

Liang, Yanyu ;

Parsana, Princy ;

Flynn, Elise ;

Fresard, Laure ;

Gamazon, Eric R. ;

Hamel, Andrew R. ;

He, Yuan ;

Hormozdiari, Farhad ;

Mohammadi, Pejman ;

Munoz-Aguirre, Manuel ;

Ardlie, Kristin G. ;

Battle, Alexis ;

Bonazzola, Rodrigo ;

Brown, Christopher D. ;

Cox, Nancy ;

Dermitzakis, Emmanouil T. ;

Engelhardt, Barbara E. ;

Garrido-Martin, Diego ;

Gay, Nicole R. ;

Getz, Gad ;

Guigo, Roderic ;

Hamel, Andrew R. ;

Handsaker, Robert E. ;

He, Yuan ;

Hoffman, Paul J. ;

Hormozdiari, Farhad ;

Im, Hae Kyung ;

Jo, Brian ;

Kasela, Silva ;

Kashin, Seva ;

Kim-Hellmuth, Sarah ;

Kwong, Alan ;

Lappalainen, Tuuli ;

Li, Xiao ;

Liang, Yanyu ;

MacArthur, Daniel G. ;

Mohammadi, Pejman ;

Montgomery, Stephen B. ;

Munoz-Aguirre, Manuel ;

Rouhana, John M. ;

Hormozdiari, Farhad ;

Im, Hae Kyung .

SCIENCE, 2020, 369 (6509) :1318-1330

[2] Cross-ancestry genome-wide meta-analysis of 61,047 cases and 947,237 controls identifies new susceptibility loci contributing to lung cancer [J].

Byun, Jinyoung ;

Han, Younghun ;

Li, Yafang ;

Xia, Jun ;

Long, Erping ;

Choi, Jiyeon ;

Xiao, Xiangjun ;

Zhu, Meng ;

Zhou, Wen ;

Sun, Ryan ;

Bosse, Yohan ;

Song, Zhuoyi ;

Schwartz, Ann ;

Lusk, Christine ;

Rafnar, Thorunn ;

Stefansson, Kari ;

Zhang, Tongwu ;

Zhao, Wei ;

Pettit, Rowland W. ;

Liu, Yanhong ;

Li, Xihao ;

Zhou, Hufeng ;

Walsh, Kyle M. ;

Gorlov, Ivan ;

Gorlova, Olga ;

Zhu, Dakai ;

Rosenberg, Susan M. ;

Pinney, Susan ;

Bailey-Wilson, Joan E. ;

Mandal, Diptasri ;

de Andrade, Mariza ;

Gaba, Colette ;

Willey, James C. ;

You, Ming ;

Anderson, Marshall ;

Wiencke, John K. ;

Albanes, Demetrius ;

Lam, Stephan ;

Tardon, Adonina ;

Chen, Chu ;

Goodman, Gary ;

Bojeson, Stig ;

Brenner, Hermann ;

Landi, Maria Teresa ;

Chanock, Stephen J. ;

Johansson, Mattias ;

Muley, Thomas ;

Risch, Angela ;

Wichmann, H-Erich ;

Bickeboeller, Heike .

NATURE GENETICS, 2022, 54 (08) :1167-+

[3] Changes in environmental exposures over decades may influence the genetic architecture of severe spermatogenic failure [J].

Cervan-Martin, Miriam ;

Gonzalez-Munoz, Sara ;

Guzman-Jimenez, Andrea ;

Higueras-Serrano, Inmaculada ;

Castilla, Jose A. ;

Garrido, Nicolas ;

Lujan, Saturnino ;

Bassas, Lluis ;

Seixas, Susana ;

Goncalves, Joao ;

Lopes, Alexandra M. ;

Larriba, Sara ;

Palomino-Morales, Rogelio J. ;

Bossini-Castillo, Lara ;

Carmona, F. David .

HUMAN REPRODUCTION, 2024, 39 (03) :612-622

[4] Immune and spermatogenesis-related loci are involved in the development of extreme patterns of male infertility [J].

Cervan-Martin, Miriam ;

Tuettelmann, Frank ;

Lopes, Alexandra M. ;

Bossini-Castillo, Lara ;

Rivera-Egea, Rocio ;

Garrido, Nicolas ;

Lujan, Saturnino ;

Romeu, Gema ;

Santos-Ribeiro, Samuel ;

Castilla, Jose A. ;

Carmen Gonzalvo, M. ;

Clavero, Ana ;

Maldonado, Vicente ;

Vicente, F. Javier ;

Gonzalez-Munoz, Sara ;

Guzman-Jimenez, Andrea ;

Burgos, Miguel ;

Jimenez, Rafael ;

Pacheco, Alberto ;

Gonzalez, Cristina ;

Gomez, Susana ;

Amoros, David ;

Aguilar, Jesus ;

Quintana, Fernando ;

Calhaz-Jorge, Carlos ;

Aguiar, Ana ;

Nunes, Joaquim ;

Sousa, Sandra ;

Pereira, Isabel ;

Pinto, Maria Graca ;

Correia, Sonia ;

Sanchez-Curbelo, Josvany ;

Lopez-Rodrigo, Olga ;

Martin, Javier ;

Pereira-Caetano, Iris ;

Marques, Patricia I. ;

Carvalho, Filipa ;

Barros, Alberto ;

Gromoll, Joerg ;

Bassas, Lluis ;

Seixas, Susana ;

Goncalves, Joao ;

Larriba, Sara ;

Kliesch, Sabine ;

Palomino-Morales, Rogelio J. ;

Carmona, F. David .

COMMUNICATIONS BIOLOGY, 2022, 5 (01)

[5] Genetic Landscape of Nonobstructive Azoospermia and New Perspectives for the Clinic [J].

Cervan-Martin, Miriam ;

Castilla, Jose A. ;

Palomino-Morales, Rogelio J. ;

David Carmona, F. .

JOURNAL OF CLINICAL MEDICINE, 2020, 9 (02)

[6] Second-generation PLINK: rising to the challenge of larger and richer datasets [J].

Chang, Christopher C. ;

Chow, Carson C. ;

Tellier, Laurent C. A. M. ;

Vattikuti, Shashaank ;

Purcell, Shaun M. ;

Lee, James J. .

GIGASCIENCE, 2015, 4

[7] PRSice-2: Polygenic Risk Score software for biobank-scale data [J].

Choi, Shing Wan ;

O'Reilly, Paul F. .

GIGASCIENCE, 2019, 8 (07)

[8]

Cooper TG, 2010, HUM REPROD UPDATE, V16, P231, DOI [10.1093/humupd/dmq020, 10.1093/humupd/dmp048]

[9] Sperm recovery and ICSI outcomes in men with non-obstructive azoospermia: a systematic review and meta-analysis [J].

Corona, Giovanni ;

Minhas, Suks ;

Giwercman, Aleksander ;

Bettocchi, Carlo ;

Dinkelman-Smit, Marij ;

Dohle, Gert ;

Fusco, Ferdinando ;

Kadioglou, Ates ;

Kliesch, Sabine ;

Kopa, Zsolt ;

Krausz, Csilla ;

Pelliccione, Fiore ;

Pizzocaro, Alessandro ;

Rassweiler, Jens ;

Verze, Paolo ;

Vignozzi, Linda ;

Weidner, Wolfgang ;

Maggi, Mario ;

Sofikitis, Nikolaos .

HUMAN REPRODUCTION UPDATE, 2019, 25 (06) :733-757

[10] Infertility prevalence and the methods of estimation from 1990 to 2021: a systematic review and meta-analysis [J].

Cox, C. M. ;

Thoma, M. E. ;

Tchangalova, N. ;

Mburu, G. ;

Bornstein, M. J. ;

Johnson, C. L. ;

Kiarie, J. .

HUMAN REPRODUCTION OPEN, 2022, 2022 (04)

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