Advancing our understanding of genetic risk factors and potential personalized strategies for pelvic organ prolapse.

Autor: Pujol-Gualdo N; Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia. natalia.pujol.gualdo@ut.ee.; Department of Obstetrics and Gynecology, PEDEGO Research Unit, Medical Research Centre, Oulu, University Hospital, University of Oulu, Oulu, Finland. natalia.pujol.gualdo@ut.ee., Läll K; Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia., Lepamets M; Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia., Rossi HR; Department of Obstetrics and Gynecology, PEDEGO Research Unit, Medical Research Centre, Oulu, University Hospital, University of Oulu, Oulu, Finland., Arffman RK; Department of Obstetrics and Gynecology, PEDEGO Research Unit, Medical Research Centre, Oulu, University Hospital, University of Oulu, Oulu, Finland., Piltonen TT; Department of Obstetrics and Gynecology, PEDEGO Research Unit, Medical Research Centre, Oulu, University Hospital, University of Oulu, Oulu, Finland., Mägi R; Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia., Laisk T; Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Jun 23; Vol. 13 (1), pp. 3584. Date of Electronic Publication: 2022 Jun 23.
DOI: 10.1038/s41467-022-31188-5
Abstrakt: Pelvic organ prolapse is a common gynecological condition with limited understanding of its genetic background. In this work, we perform a genome-wide association meta-analysis comprising 28,086 cases and 546,291 controls from European ancestry. We identify 19 novel genome-wide significant loci, highlighting connective tissue, urogenital and cardiometabolic as likely affected systems. Here, we prioritize many genes of potential interest and assess shared genetic and phenotypic links. Additionally, we present the first polygenic risk score, which shows similar predictive ability (Harrell C-statistic (C-stat) 0.583, standard deviation (sd) = 0.007) as five established clinical risk factors combined (number of children, body mass index, ever smoked, constipation and asthma) (C-stat = 0.588, sd = 0.007) and demonstrates a substantial incremental value in combination with these (C-stat = 0.630, sd = 0.007). These findings improve our understanding of genetic factors underlying pelvic organ prolapse and provide a solid start evaluating polygenic risk scores as a potential tool to enhance individual risk prediction.
(© 2022. The Author(s).)
Databáze: MEDLINE
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