Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
Department of Obstetrics and Gynecology, PEDEGO Research Unit, Medical Research Centre, Oulu, University Hospital, University of Oulu, Oulu, Finland.
Nat Commun. 2022 Jun 23;13(1):3584. doi: 10.1038/s41467-022-31188-5.
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.
盆腔器官脱垂是一种常见的妇科疾病，其遗传背景的了解有限。在这项工作中，我们进行了一项全基因组关联荟萃分析，纳入了来自欧洲血统的 28086 例病例和 546291 例对照。我们确定了 19 个新的全基因组显著位点，突出了结缔组织、泌尿生殖和心血管代谢系统可能受到影响。在这里，我们优先考虑了许多具有潜在重要性的基因，并评估了它们的共同遗传和表型联系。此外，我们提出了第一个多基因风险评分，其表现出类似的预测能力（Harrell C 统计量（C 统计量）为 0.583，标准偏差（sd）= 0.007），与五个已建立的临床危险因素（孩子数量、体重指数、是否吸烟、便秘和哮喘）相结合（C 统计量为 0.588，sd = 0.007），并在与这些危险因素结合时显示出显著的增量价值（C 统计量为 0.630，sd = 0.007）。这些发现增进了我们对盆腔器官脱垂遗传基础的理解，并为评估多基因风险评分作为增强个体风险预测的潜在工具提供了坚实的基础。
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