A comprehensive study of common and rare genetic variants in spermatogenesis-related loci identifies new risk factors for idiopathic severe spermatogenic failure
STUDY QUESTION: Can genome-wide genotyping data be analysed using a hypothesis-driven approach to enhance the understanding of the genetic basis of severe spermatogenic failure (SPGF) in male infertility? SUMMARY ANSWER: Our findings revealed a significant association between SPGF and the SHOC1 gene...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2024 |
| País: | España |
| Institución: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:ddd.uab.cat:310171 |
| Acceso en línea: | https://ddd.uab.cat/record/310171 https://dx.doi.org/urn:doi:10.1093/hropen/hoae069 |
| Access Level: | acceso abierto |
| Palabra clave: | Genetics Idiopathic spermatogenic failure Male infertility Monogenic mutations Polygenic susceptibility Spermatogenesis |
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A comprehensive study of common and rare genetic variants in spermatogenesis-related loci identifies new risk factors for idiopathic severe spermatogenic failureGuzmán-Jiménez, Andrea|||0000-0002-2091-0568González-Muñoz, SaraCerván-Martín, Miriam|||0000-0001-6033-0587Garrido, Nicolás|||0000-0001-8271-5218Castilla, José Antonio|||0000-0003-2185-565XGonzálvo, María CarmenClavero, AnaMolina, MartaLuján, Saturnino|||0000-0002-5005-3325Santos-Ribeiro, Samuel|||0000-0003-2476-7858Vilches, Miguel Angel|||0000-0002-5533-437XEspuch, AndreaMaldonado, Vicente|||0000-0003-4456-7191Galiano-Gutiérrez, NoeliaSantamaría-López, EstherGonzález-Ravina, CristinaQuintana-Ferraz, FernandoGómez, SusanaAmorós, DavidMartínez-Granados, LuisOrtega-González, YaniraBurgos, Miguel|||0000-0003-4446-9313Pereira-Caetano, IrisBulbul, OzgurCastellano, StefanoRomano, MassimoAlbani, ElenaBassas, Lluís|||0000-0002-3473-3611Seixas, Susana|||0000-0002-7035-7422Gonçalves, João|||0000-0001-9359-8774Lopes, Alexandra M.|||0000-0003-3539-2318Larriba, Sara|||0000-0003-4579-5452Palomino-Morales, Rogelio J.|||0000-0003-3507-343XCarmona, F. David|||0000-0002-1427-7639Bossini-Castillo, Lara|||0000-0002-5471-5824GeneticsIdiopathic spermatogenic failureMale infertilityMonogenic mutationsPolygenic susceptibilitySpermatogenesisSTUDY QUESTION: Can genome-wide genotyping data be analysed using a hypothesis-driven approach to enhance the understanding of the genetic basis of severe spermatogenic failure (SPGF) in male infertility? SUMMARY ANSWER: Our findings revealed a significant association between SPGF and the SHOC1 gene and identified three novel genes (PCSK4, AP3B1, and DLK1) along with 32 potentially pathogenic rare variants in 30 genes that contribute to this condition. WHAT IS KNOWN ALREADY: SPGF is a major cause of male infertility, often with an unknown aetiology. SPGF can be due to either multifactorial causes, including both common genetic variants in multiple genes and environmental factors, or highly damaging rare variants. Next-generation sequencing methods are useful for identifying rare mutations that explain monogenic forms of SPGF. Genome-wide association studies (GWASs) have become essential approaches for deciphering the intricate genetic landscape of complex diseases, offering a cost-effective and rapid means to genotype millions of genetic variants. Novel methods have demonstrated that GWAS datasets can be used to infer rare coding variants that are causal for male infertility phenotypes. However, this approach has not been previously applied to characterize the genetic component of a whole case-control cohort. STUDY DESIGN, SIZE, DURATION: We employed a hypothesis-driven approach focusing on all genetic variation identified, using a GWAS platform and subsequent genotype imputation, encompassing over 20 million polymorphisms and a total of 1571 SPGF patients and 2431 controls. Both common (minor allele frequency, MAF.Universitat Autònoma de Barcelona 22024-01-0120242024-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/310171https://dx.doi.org/urn:doi:10.1093/hropen/hoae069reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengAgencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2020-120157RB-I00Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2021/SGR-052open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:3101712026-06-06T12:50:31Z |
| dc.title.none.fl_str_mv |
A comprehensive study of common and rare genetic variants in spermatogenesis-related loci identifies new risk factors for idiopathic severe spermatogenic failure |
| title |
A comprehensive study of common and rare genetic variants in spermatogenesis-related loci identifies new risk factors for idiopathic severe spermatogenic failure |
| spellingShingle |
A comprehensive study of common and rare genetic variants in spermatogenesis-related loci identifies new risk factors for idiopathic severe spermatogenic failure Guzmán-Jiménez, Andrea|||0000-0002-2091-0568 Genetics Idiopathic spermatogenic failure Male infertility Monogenic mutations Polygenic susceptibility Spermatogenesis |
| title_short |
A comprehensive study of common and rare genetic variants in spermatogenesis-related loci identifies new risk factors for idiopathic severe spermatogenic failure |
| title_full |
A comprehensive study of common and rare genetic variants in spermatogenesis-related loci identifies new risk factors for idiopathic severe spermatogenic failure |
| title_fullStr |
A comprehensive study of common and rare genetic variants in spermatogenesis-related loci identifies new risk factors for idiopathic severe spermatogenic failure |
| title_full_unstemmed |
A comprehensive study of common and rare genetic variants in spermatogenesis-related loci identifies new risk factors for idiopathic severe spermatogenic failure |
| title_sort |
A comprehensive study of common and rare genetic variants in spermatogenesis-related loci identifies new risk factors for idiopathic severe spermatogenic failure |
| dc.creator.none.fl_str_mv |
Guzmán-Jiménez, Andrea|||0000-0002-2091-0568 González-Muñoz, Sara Cerván-Martín, Miriam|||0000-0001-6033-0587 Garrido, Nicolás|||0000-0001-8271-5218 Castilla, José Antonio|||0000-0003-2185-565X Gonzálvo, María Carmen Clavero, Ana Molina, Marta Luján, Saturnino|||0000-0002-5005-3325 Santos-Ribeiro, Samuel|||0000-0003-2476-7858 Vilches, Miguel Angel|||0000-0002-5533-437X Espuch, Andrea Maldonado, Vicente|||0000-0003-4456-7191 Galiano-Gutiérrez, Noelia Santamaría-López, Esther González-Ravina, Cristina Quintana-Ferraz, Fernando Gómez, Susana Amorós, David Martínez-Granados, Luis Ortega-González, Yanira Burgos, Miguel|||0000-0003-4446-9313 Pereira-Caetano, Iris Bulbul, Ozgur Castellano, Stefano Romano, Massimo Albani, Elena Bassas, Lluís|||0000-0002-3473-3611 Seixas, Susana|||0000-0002-7035-7422 Gonçalves, João|||0000-0001-9359-8774 Lopes, Alexandra M.|||0000-0003-3539-2318 Larriba, Sara|||0000-0003-4579-5452 Palomino-Morales, Rogelio J.|||0000-0003-3507-343X Carmona, F. David|||0000-0002-1427-7639 Bossini-Castillo, Lara|||0000-0002-5471-5824 |
| author |
Guzmán-Jiménez, Andrea|||0000-0002-2091-0568 |
| author_facet |
Guzmán-Jiménez, Andrea|||0000-0002-2091-0568 González-Muñoz, Sara Cerván-Martín, Miriam|||0000-0001-6033-0587 Garrido, Nicolás|||0000-0001-8271-5218 Castilla, José Antonio|||0000-0003-2185-565X Gonzálvo, María Carmen Clavero, Ana Molina, Marta Luján, Saturnino|||0000-0002-5005-3325 Santos-Ribeiro, Samuel|||0000-0003-2476-7858 Vilches, Miguel Angel|||0000-0002-5533-437X Espuch, Andrea Maldonado, Vicente|||0000-0003-4456-7191 Galiano-Gutiérrez, Noelia Santamaría-López, Esther González-Ravina, Cristina Quintana-Ferraz, Fernando Gómez, Susana Amorós, David Martínez-Granados, Luis Ortega-González, Yanira Burgos, Miguel|||0000-0003-4446-9313 Pereira-Caetano, Iris Bulbul, Ozgur Castellano, Stefano Romano, Massimo Albani, Elena Bassas, Lluís|||0000-0002-3473-3611 Seixas, Susana|||0000-0002-7035-7422 Gonçalves, João|||0000-0001-9359-8774 Lopes, Alexandra M.|||0000-0003-3539-2318 Larriba, Sara|||0000-0003-4579-5452 Palomino-Morales, Rogelio J.|||0000-0003-3507-343X Carmona, F. David|||0000-0002-1427-7639 Bossini-Castillo, Lara|||0000-0002-5471-5824 |
| author_role |
author |
| author2 |
González-Muñoz, Sara Cerván-Martín, Miriam|||0000-0001-6033-0587 Garrido, Nicolás|||0000-0001-8271-5218 Castilla, José Antonio|||0000-0003-2185-565X Gonzálvo, María Carmen Clavero, Ana Molina, Marta Luján, Saturnino|||0000-0002-5005-3325 Santos-Ribeiro, Samuel|||0000-0003-2476-7858 Vilches, Miguel Angel|||0000-0002-5533-437X Espuch, Andrea Maldonado, Vicente|||0000-0003-4456-7191 Galiano-Gutiérrez, Noelia Santamaría-López, Esther González-Ravina, Cristina Quintana-Ferraz, Fernando Gómez, Susana Amorós, David Martínez-Granados, Luis Ortega-González, Yanira Burgos, Miguel|||0000-0003-4446-9313 Pereira-Caetano, Iris Bulbul, Ozgur Castellano, Stefano Romano, Massimo Albani, Elena Bassas, Lluís|||0000-0002-3473-3611 Seixas, Susana|||0000-0002-7035-7422 Gonçalves, João|||0000-0001-9359-8774 Lopes, Alexandra M.|||0000-0003-3539-2318 Larriba, Sara|||0000-0003-4579-5452 Palomino-Morales, Rogelio J.|||0000-0003-3507-343X Carmona, F. David|||0000-0002-1427-7639 Bossini-Castillo, Lara|||0000-0002-5471-5824 |
| author2_role |
author author author author author author author author author author author author author 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 |
Universitat Autònoma de Barcelona |
| dc.subject.none.fl_str_mv |
Genetics Idiopathic spermatogenic failure Male infertility Monogenic mutations Polygenic susceptibility Spermatogenesis |
| topic |
Genetics Idiopathic spermatogenic failure Male infertility Monogenic mutations Polygenic susceptibility Spermatogenesis |
| description |
STUDY QUESTION: Can genome-wide genotyping data be analysed using a hypothesis-driven approach to enhance the understanding of the genetic basis of severe spermatogenic failure (SPGF) in male infertility? SUMMARY ANSWER: Our findings revealed a significant association between SPGF and the SHOC1 gene and identified three novel genes (PCSK4, AP3B1, and DLK1) along with 32 potentially pathogenic rare variants in 30 genes that contribute to this condition. WHAT IS KNOWN ALREADY: SPGF is a major cause of male infertility, often with an unknown aetiology. SPGF can be due to either multifactorial causes, including both common genetic variants in multiple genes and environmental factors, or highly damaging rare variants. Next-generation sequencing methods are useful for identifying rare mutations that explain monogenic forms of SPGF. Genome-wide association studies (GWASs) have become essential approaches for deciphering the intricate genetic landscape of complex diseases, offering a cost-effective and rapid means to genotype millions of genetic variants. Novel methods have demonstrated that GWAS datasets can be used to infer rare coding variants that are causal for male infertility phenotypes. However, this approach has not been previously applied to characterize the genetic component of a whole case-control cohort. STUDY DESIGN, SIZE, DURATION: We employed a hypothesis-driven approach focusing on all genetic variation identified, using a GWAS platform and subsequent genotype imputation, encompassing over 20 million polymorphisms and a total of 1571 SPGF patients and 2431 controls. Both common (minor allele frequency, MAF. |
| publishDate |
2024 |
| dc.date.none.fl_str_mv |
2 2024-01-01 2024 2024-01-01 |
| dc.type.none.fl_str_mv |
Article http://purl.org/coar/resource_type/c_6501 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
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article |
| dc.identifier.none.fl_str_mv |
https://ddd.uab.cat/record/310171 https://dx.doi.org/urn:doi:10.1093/hropen/hoae069 |
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https://ddd.uab.cat/record/310171 https://dx.doi.org/urn:doi:10.1093/hropen/hoae069 |
| dc.language.none.fl_str_mv |
Inglés eng |
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Inglés |
| language |
eng |
| dc.relation.none.fl_str_mv |
Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2020-120157RB-I00 Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2021/SGR-052 |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
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openAccess |
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application/pdf |
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reponame:Dipòsit Digital de Documents de la UAB instname:Universitat Autònoma de Barcelona |
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Universitat Autònoma de Barcelona |
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