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Lipid metabolism and neuromuscular junction as common pathways underlying the genetic basis of erectile dysfunction and obstructive sleep apnea

International Journal of Impotence Research (2023)Cite this article

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Abstract

Erectile dysfunction (ED) incidence is higher in patients with obstructive sleep apnea (OSA). Studies have suggested that ED and OSA may activate similar pathways; however, few have investigated the links between their underlying genotypic profiles. Therefore, we conducted an in-silico analysis to test whether ED and OSA share genetic variants of risk and to identify any molecular, cellular and biological interactions between them. Two gene lists were manually curated through a literature review based on a PUBMED search, which resulted in one gene list associated with ED (total of 205 genes) and the other with OSA (total of 2622 genes). Between those gene sets, 35 were common for both lists (Fisher exact test, p-value = 0.027). The Protein–protein interaction (PPI) analysis using the intersect list as input showed that 3 of them had direct interactions (LPL, DGKB and PLCB1). In addition, the biological function of the genes contained in the intersect list suggested that pathways related to lipid metabolism and the neuromuscular junction were commonly found in the genetic basis of ED and OSA. From the shared genes between both conditions, the biological pathways highlighted in this study may serve as preliminary findings for future functional investigations on OSA and ED association.

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Fig. 1: The intersection of studied genes.
Fig. 2: The mainly enriched biological pathways of intersection list of genes.
Fig. 3: PPI network interaction between intersecting gene lists. Network showing 12 OSA and ED-associated genes (green) plus 9 interactors (purple).
Fig. 4: Mechanistic hypothesis.

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Data availability

Gene lists were generated from previous published genetic studies, which are fully described in Supplementary Table 1.

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Acknowledgements

This work was supported by Associação Fundo de Incentivo à Pesquisa and grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, recipients: LNGA: 2023/11995-5; MMO: 2021/09089-0; MLA: 2020/13467-8), and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, recipient: MLA and LNGA).

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Authors and Affiliations

  1. Sleep Institute, São Paulo, Brazil

    Luana N. G. Adami, Mariana Moysés-Oliveira, Lais Amanda Souza-Cunha, Sergio Tufik & Monica L. Andersen

  2. Departamento de Psicobiologia, Universidade Federal de São Paulo, São Paulo, Brazil

    Luana N. G. Adami, Sergio Tufik & Monica L. Andersen

  3. Departamento de Cirurgia, Disciplina de Urologia, Universidade Federal de São Paulo, São Paulo, Brazil

    Matheus Brandão Vasco

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Contributions

LNGA manually curated the gene lists. LNGA, MMO and LASC performed data analysis. MLA and ST supervised and provided funding to the study. MBV performed the literature review about erectile dysfunction. LNGA drafted the manuscript. All authors revised the manuscript.

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Correspondence to Monica L. Andersen.

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41443_2023_795_MOESM1_ESM.pdf

Supplementary Table 1. Lists of articles regarding Erectile Dysfunction (ED) and Obstructive Sleep Apnea traits (OSA) which were used in this study.

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Adami, L.N.G., Moysés-Oliveira, M., Souza-Cunha, L.A. et al. Lipid metabolism and neuromuscular junction as common pathways underlying the genetic basis of erectile dysfunction and obstructive sleep apnea. Int J Impot Res (2023). https://doi.org/10.1038/s41443-023-00795-1

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  • DOI: https://doi.org/10.1038/s41443-023-00795-1

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