@misc{10481/78210,
year = {2022},
month = {11},
url = {https://hdl.handle.net/10481/78210},
abstract = {We conducted a genome-wide association study in a large population of infertile men due to unexplained spermatogenic failure (SPGF). More than seven million genetic variants were analysed in 1,274 SPGF cases and 1,951 unaffected controls from two independent European cohorts. Two genomic regions were associated with the most severe histological pattern of SPGF, defined by Sertoli cell-only (SCO) phenotype, namely the MHC class II gene HLA-DRB1 (rs1136759, P = 1.32E-08, OR = 1.80) and an upstream locus of VRK1 (rs115054029, P = 4.24E-08, OR = 3.14), which encodes a protein kinase involved in the regulation of spermatogenesis. The SCO-associated rs1136759 allele (G) determines a serine in the position 13 of the HLA-DRβ1 molecule located in the antigen-binding pocket. Overall, our data support the notion of unexplained SPGF as a complex trait influenced by common variation in the genome, with the SCO phenotype likely representing an immune-mediated condition.},
organization = {Andalusian Plan for Research and Innovation},
organization = {Juan de la Cierva Incorporación	IJC2018-038026-I},
organization = {Ministry for Science, Technology and High Education},
organization = {BES-2017-081222, MCIN/AEI/10.13039/501100011033},
organization = {National Funds	IF/01262/2014, PEstC/SAU/LA0003/2013, POCI-01-0145-FEDER-007274, SFRH/BPD/120777/2016},
organization = {PAIDI 2020	PY20_00212},
organization = {R+D+i Projects	B-CTS-584-UGR20, RYC-2014-16458},
organization = {Faculty of Science and Engineering, University of Manchester
 
	

FPU20/02926},
organization = {Deutsche Forschungsgemeinschaft

	

DFG CRU326},
organization = {Fundação para a Ciência e a Tecnologia},
organization = {Generalitat de Catalunya

	

2017SGR191},
organization = {Ministerio de Economía y Competitividad},
organization = {Instituto de Salud Carlos III

	

DTS18/00101},
organization = {Ministerio de Ciencia e Innovación},
organization = {European Social Fund

UIDB/UIDP/00009/2020},
organization = {European Regional Development Fund},
organization = {Fundació Catalana de Trasplantament},
organization = {Departament de Salut, Generalitat de Catalunya

	

CES09/020},
organization = {Programa Operacional Temático Factores de Competitividade},
organization = {Spanish National Plan for Scientific and Technical Research and Innovation

	

PID2020-120157RB-I00, SAF2016-78722-R},
publisher = {Springer Nature},
title = {Immune and spermatogenesis-related loci are involved in the development of extreme patterns of male infertility},
doi = {10.1038/s42003-022-04192-0},
author = {Cerván Martín, Miriam and Bossini Castillo, Lara María and González Muñoz, Sara and Guzmán Jiménez, Andrea and Burgos Poyatos, Miguel and Jiménez Medina, Rafael and Palomino Morales, Rogelio Jesús and Carmona López, Francisco David},
}