A Molecular Landscape of Stress Urinary Incontinence in Women Suggests an Important Role of Beta-Catenin Signaling in Disease Etiology

Abstract

Purpose: Stress urinary incontinence (SUI) represents a major health burden in women, but a thorough understanding of the underlying molecular mechanisms is lacking. Our aim was to further elucidate these mechanisms to ultimately find new treatments. Materials and Methods: This study integrated the most significant genes from 4 genome-wide association studies (GWASs) of SUI in women with other genetic, expression, and/or functional evidence from the literature into a molecular landscape. A network enrichment analysis of the top SUI GWAS genes was conducted, followed by an extensive literature search to identify interactions between the proteins encoded by the GWAS genes and proteins/molecules implicated in SUI through other evidence. Results: In total, 188 GWAS genes were used for network enrichment analysis that yielded 12 networks, of which 8 were overlapping, with beta-catenin as the central protein. Based on this finding and our literature search, we built a molecular landscape of female SUI that centers on beta-catenin signaling. Other important functional landscape themes are epithelial-mesenchymal transition, NANOG signaling, and female sex hormone signaling. Conclusions: The molecular landscape of female SUI that we built based on genetic data provides novel molecular insights that may be instrumental for better understanding the etiology of SUI and developing novel SUI treatments.