Urinary incontinence (UI) affects more than half of adult women in the US, while fecal incontinence (FI) may affect up to 20% of elderly women in the US. Epidemiologic studies have identified demographic, lifestyle, and medical risk factors for these conditions. However, in addition to these known risk factors, we hypothesize that there are genetic variants that predispose women to developing UI and FI. We previously generated genome-wide single nucleotide polymorphism data from participants in the Nurses' Health Study who were selected as cases or controls for many disease outcomes. These participants have also provided extensive, longitudinal information on health outcomes, including UI and FI. Thus, the goal of this project is to utilize existing genetic data from 12,123 women for whom we have questionnaire responses and clinical information to evaluate the association of inherited genetic variation with stress, urgency, and mixed UI subtypes and with FI. We will identify genetic variants and pathways that are associated with these outcomes, and begin to explore their function using publicly available data. There are several potential benefits of this study. Identifying genetic variants could help elucidate biologic mechanisms and enhance risk prediction models for these conditions. Improved understanding of the genes and pathways influencing risk will aid in efforts to develop interventions, and allow for the measurement of influential variants in future clinical studies. In addition, we anticipate the findings of this research will lead to future large-scale studies in these cohorts to understand the impact of significant genetic variants on the associations of lifestyle and treatment with these outcomes. In future studies, we will also be able to examine the association of these genetic variants with various types of biological specimen data in our cohorts, including gene expression, metabolomics, and microbiomics, which will provide a more comprehensive understanding of the underlying biology of the conditions. Overall, this research proposal provides an opportunity to investigate the understudied genetic aspects of these conditions to improve our understanding of their etiology and, ultimately, reduce their burden among women.
Urinary and fecal incontinence are common conditions that affect a large percentage of women and greatly decrease quality of life. This project will perform genome-wide association studies for these conditions using large genetic datasets from the well-characterized Nurses' Health Study. We will also examine genetic variation across biological pathways and explore the possible function of significant variants to more comprehensively address the role of genetics. Identifying genetic variants that predispose individuals to these conditions will improve understanding of their etiology, potentially leading to the development of better interventions and treatments.
