ArticleThe Journal of clinical endocrinology and metabolism2022
A GWAS in Idiopathic/Unexplained Infertile Men Detects a Genomic Region Determining Follicle-Stimulating Hormone Levels.
Article in The Journal of clinical endocrinology and metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 11 citations in OpenAlex.
- Can Hormonal Therapy Improve the Outcomes of mTESE in Patients With Non-Obstructive Azoospermia?Andrology · 2026Article
- BMI-Dependent Correlations of Sex Hormone Genes with Simple Endometrial Hyperplasia.Life (Basel, Switzerland) · 2026Article
- Polymorphism of theLife (Basel, Switzerland) · 2026Article
- Review
- Statistical methods to disentangle genetic effects influencing infertility and early fetal viability with a genome-wide application.PLoS genetics · 2025Article
- Genome-Wide Association Analyses in Family Triads and Dyads Following Assisted Reproductive Technology.Genetic epidemiology · 2025Article
- FSH Therapy in Male Factor Infertility: Evidence and Factors Which Might Predict the Response.Life (Basel, Switzerland) · 2024Review
- Translational Bioinformatics for Human Reproductive Biology Research: Examples, Opportunities and Challenges for a Future Reproductive Medicine.International journal of molecular sciences · 2022Review
- A GWAS in Idiopathic/Unexplained Infertile Men Detects a Genomic Region Determining Follicle-Stimulating Hormone Levels.The Journal of clinical endocrinology and metabolism · 2022Article
- Hormonal Therapy Before Sperm Retrieval in Men With Non-Obstructive Azoospermia: From Controversy to Precision Using the APHRODITE Criteria.Reproductive medicine and biologyReview
- Inflammation and Oxidative Stress in Male Infertility: A Narrative Review.Reproductive medicine and biologyReview
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
contextApproximately 70% of infertile men are diagnosed with idiopathic (abnormal semen parameters) or unexplained (normozoospermia) infertility, with the common feature of lacking etiologic factors. Follicle-stimulating hormone (FSH) is essential for initiation and maintenance of spermatogenesis. Certain single-nucleotide variations (SNVs; formerly single-nucleotide polymorphisms [SNPs]) (ie, FSHB c.-211G > T, FSHR c.2039A > G) are associated with FSH, testicular volume, and spermatogenesis. It is unknown to what extent other variants are associated with FSH levels and therewith resemble causative factors for infertility.
objectiveWe aimed to identify further genetic determinants modulating FSH levels in a cohort of men presenting with idiopathic or unexplained infertility.
methodsWe 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.
resultsImputation 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.
conclusionsThis 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.
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