We aimed to identify further genetic determinants modulating FSH levels in a cohort of men presenting with idiopathic or unexplained infertility.
We retrospectively (2010-2018) selected 1900 men with idiopathic/unexplained infertility. In the discovery study (n = 760), a genome-wide association study (GWAS) was performed (Infinium PsychArrays) in association with FSH values (Illumina GenomeStudio, v2.0). Minor allele frequencies (MAFs) were analyzed for the discovery and an independent normozoospermic cohort. In the validation study (n = 1140), TaqMan SNV polymerase chain reaction was conducted for rs11031005 and rs10835638 in association with andrological parameters.
Imputation revealed 9 SNVs in high linkage disequilibrium, with genome-wide significance (P < 4.28e-07) at the FSHB locus 11p.14.1 being associated with FSH. The 9 SNVs accounted for up to a 4.65% variance in FSH level. In the oligozoospermic subgroup, this was increased up to 6.95% and the MAF was enhanced compared to an independent cohort of normozoospermic men. By validation, a significant association for rs11031005/rs10835638 with FSH (P = 4.71e-06/5.55e-07) and FSH/luteinizing hormone ratio (P = 2.08e-12/6.4e-12) was evident.
This GWAS delineates the polymorphic FSHB genomic region as the main determinant of FSH levels in men with unexplained or idiopathic infertility. Given the essential role of FSH, molecular detection of one of the identified SNVs that causes lowered FSH and therewith decreases spermatogenesis could resolve the idiopathic/unexplained origin by this etiologic factor.
我们的目的是在一组患有特发性或无法解释的不孕症的男性中进一步确定调节FSH水平的遗传决定因素。
我们回顾性地(2010-2018年)选择了1900名特发性/无法解释的不孕症男性。
归因显示9个SNV处于高连锁不平衡状态,
这个GWAS描述了多态性FSHB基因组区域是不明原因或特发性不育症男性FSH水平的主要决定因素。