Dataset Information

Syndromic male subfertility: A network view of genome-phenome associations.

ABSTRACT:

Background

Male infertility is a disorder of the reproductive system with a highly complex genetic landscape. In most cases, the reason for male infertility remains unknown; however, the importance of genetic abnormalities in the diagnosis of subfertility/infertility is becoming increasingly recognized. Several syndromes include impaired male fertility in the clinical picture, although a comprehensive analysis of genetic causes of the syndromology perspective of male reproduction is not yet available.

Objectives

(1) To develop a catalog of syndromes and corresponding genes associated with impaired male fertility and (2) to visualize an up-to-date genome-phenome network of syndromic male subfertility.

Materials and methods

Published literature was retrieved from the Online Mendelian Inheritance in Man, Orphanet, Human Phenotype Ontology and PubMed databases using keywords "male infertility," "syndrome," "gene," and "case report"; time period from 1980 to September, 2021. Retrieved data were organized as a catalog and complemented with identification numbers of syndromes (MIM ID) and genes (Gene ID). The genome-phenome network and the phenome network were visualized using Cytoscape and Gephi software platforms. Protein-protein interaction analysis was performed using STRING tool.

Results

Retrieved syndromes were presented as (1) a catalog containing 63 syndromes and 93 associated genes, (2) a genome-phenome network including CHD7 and WT1 genes and Noonan and Kartagener syndromes, and (3) a phenome network including 63 syndromes, and 25 categories of clinical features.

Discussion

The developed catalog will contribute to the advances and translational impact toward understanding the factors of syndromic male infertility. Visualized networks provide simple, flexible tools for clinicians and researchers to quickly generate hypotheses and gain a deeper understanding of underlying mechanisms affecting male reproduction.

Conclusion

Recognition of the significance of genome-phenome visualization as part of network medicine can help expedite efforts toward unravelling molecular mechanisms and enable advances personal/precision medicine of male reproduction and other complex traits.

SUBMITTER: Mikec S

PROVIDER: S-EPMC9314622 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundAn association between male subfertility and an increased risk of testicular cancer has been proposed, but conflicting results of research on this topic have rendered this theory equivocal. To more precisely assess the association between subfertility and the risk of testicular cancer, we performed a systematic review of international epidemiologic evidence.Principal findingsWe searched the Medline database for records from January 1966 to March 2008 complemented with manual searches of the literature and then identified studies that met our inclusion criteria. Study design, sample size, exposure to subfertility and risk estimates of testicular cancer incidence were abstracted. Summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated using the DerSimonian and Laird model. All statistical tests were two-sided. We identified seven case-control studies and two cohort studies published between 1987 and 2005. Analysis of the seven case-control studies that included 4,954 participants revealed an overall statistically significant association between subfertility and increased risk of testicular cancer (summary RR = 1.68, 95% CI: 1.22 to 2.31), without heterogeneity between studies (Q = 8.46, P heterogeneity = 0.21, I(2) statistics = 0.29). The association between subfertility and testicular cancer was somewhat stronger in the United States (summary RR = 1.75, 95% CI: 1.01 to 3.02) than it was in Europe (summary RR = 1.53, 95% CI: 1.22 to 1.92). The source of the control subjects had a statistically significant effect on the magnitude of the association (population-based summary-RR = 2.15, 95% CI: 1.11 to 4.17; hospital-based summary--RR = 1.56, 95% CI: 0.93 to 2.61). After excluding possible cryptorchidism, an important confounding factor, we also found a positive association between subfertility and increased risk of testicular cancer (summary RR = 1.59, 95% CI: 1.28 to 1.98). These results were consistent between studies conducted in the United States and in Europe (Q = 0.20, P heterogeneity = 0.66). Of the two cohort studies that reported standardized incidence ratios, both reported a statistically significant positive association between subfertility and increased risk of testicular cancer.ConclusionsOur findings support a relationship between subfertility and increased risk of testicular cancer and apply to the management of men with subfertility, and prevention and diagnosis of testicular cancer.