Immune and spermatogenesis-related loci are involved in the development of extreme patterns of male infertility.
Miriam Cerván-MartínFrank TüttelmannAlexandra M LopesLara Bossini-CastilloRocío Rivera-EgeaNicolás GarridoSaturnino LujanGema RomeuSamuel Santos-RibeiroJose Antonio CastillaM Carmen GonzalvoAna ClaveroVicente MaldonadoF Javier VicenteSara González-MuñozAndrea Guzmán-JiménezMiguel BurgosRafael JiménezAlberto PachecoCristina GonzálezSusana GómezDavid AmorósJesus AguilarFernando QuintanaCarlos Calhaz-JorgeAna AguiarJoaquim NunesSandra SousaIsabel PereiraMaria Graça PintoSónia CorreiaJosvany Sánchez-CurbeloOlga López-RodrigoJavier MartínIris Pereira-CaetanoPatricia I MarquesFilipa CarvalhoAlberto BarrosJörg GromollLluís BassasSusana SeixasJoão GonçalvesSara LarribaSabine KlieschRogelio J Palomino-MoralesFrancisco David CarmonaPublished in: Communications biology (2022)
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.
Keyphrases
- genome wide association study
- genome wide
- protein kinase
- copy number
- polycystic ovary syndrome
- single cell
- dna methylation
- cell therapy
- early onset
- electronic health record
- climate change
- stem cells
- metabolic syndrome
- adipose tissue
- machine learning
- binding protein
- mesenchymal stem cells
- dna binding
- genome wide identification
- editorial comment