Work

From polygenic risk to functional genomics: a framework for precision gynecological disease modeling

Year: 2026

Type: article

Abstract: Gynecological conditions including endometriosis, polyendocrine metabolic ovarian syndrome and malignancies cause widespread chronic morbidity and infertility, yet translating genetic discoveries into biological mechanisms remains challenging. We propose a framework integrating biobank-derived human genetic data, patient-derived stem cell models, and advanced tissue engineering. By combining naturally occurring genetic variation with targeted genome engineering and high-resolution molecular analyses, this approach promises to enable mechanistic insights and therapeutic discovery. We discuss methodological, ethical, and translational challenges, including polygenic risk score construction, variant prioritization, ancestry-related limitations, and modeling hormonal microenvironments. Together, this framework offers a roadmap for advancing functional genomics and precision medicine across gynecological diseases.

Source: Nature Communications

DOI: 10.1038/s41467-026-77342-1

Authors: Masuma Khatun, Juha S. Tapanainen, Andres Salumets

Institutions: University of Helsinki, Helsinki University Hospital, University of Tartu, Karolinska University Hospital, Karolinska Institutet

Language: English

Topic: Genetic Associations and Epidemiology

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $6,990