International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics · 2026
Genetic evidence for causal associations of thrombohemostasis and anticoagulant drug targets with miscarriage.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Zhang Qinyi, Yu Sihui, Wu Hao, Zhang Jiawen
Аннотация
OBJECTIVE: The causal relevance of thrombohemostatic factors and anticoagulant drug targets to miscarriage remains unclear. This study aims to systematically evaluate their potential causal effects on miscarriage phenotypes using Mendelian randomization (MR) analysis.
METHODS: We conducted a multidimensional MR study leveraging summary-level genome-wide association study (GWAS) data from individuals of European ancestry to systematically evaluate the potential causal effects of 36 thrombohemostatic factors, long-term anticoagulant use, and genetic targets of aspirin and heparin on four miscarriage phenotypes, including sporadic, spontaneous, and recurrent miscarriage, as well as bleeding in early pregnancy. Analyses included linkage disequilibrium score regression for genetic correlation, two-sample MR for causal inference, drug target MR using cis-acting genetic variants, and summary-data-based MR. Sensitivity analyses addressed pleiotropy and heterogeneity, and multiple testing was rigorously controlled.
RESULTS: No significant genetic correlation or causal association was found between thrombohemostatic factors or anticoagulant use and the risk of miscarriage after correction for multiple comparisons. Similarly, collective genetic proxies for aspirin and heparin targets showed no association with miscarriage risk. Notably, only genetically elevated expression of FGF2, a heparin target, was associated with an increased risk of spontaneous miscarriage (β = 0.277, P = 0.0017, FDR q = 0.015). Other nominal findings did not withstand correction for multiple testing. Sensitivity analyses affirmed the robustness of the primary results.
CONCLUSION: These findings do not support a causal role for thrombohemostatic factors or routine anticoagulant therapy in miscarriage prevention, underscoring the complexity of miscarriage etiology. Precision medicine approaches based on validated biomarkers might be necessary to identify women most likely to benefit from targeted interventions.
METHODS: We conducted a multidimensional MR study leveraging summary-level genome-wide association study (GWAS) data from individuals of European ancestry to systematically evaluate the potential causal effects of 36 thrombohemostatic factors, long-term anticoagulant use, and genetic targets of aspirin and heparin on four miscarriage phenotypes, including sporadic, spontaneous, and recurrent miscarriage, as well as bleeding in early pregnancy. Analyses included linkage disequilibrium score regression for genetic correlation, two-sample MR for causal inference, drug target MR using cis-acting genetic variants, and summary-data-based MR. Sensitivity analyses addressed pleiotropy and heterogeneity, and multiple testing was rigorously controlled.
RESULTS: No significant genetic correlation or causal association was found between thrombohemostatic factors or anticoagulant use and the risk of miscarriage after correction for multiple comparisons. Similarly, collective genetic proxies for aspirin and heparin targets showed no association with miscarriage risk. Notably, only genetically elevated expression of FGF2, a heparin target, was associated with an increased risk of spontaneous miscarriage (β = 0.277, P = 0.0017, FDR q = 0.015). Other nominal findings did not withstand correction for multiple testing. Sensitivity analyses affirmed the robustness of the primary results.
CONCLUSION: These findings do not support a causal role for thrombohemostatic factors or routine anticoagulant therapy in miscarriage prevention, underscoring the complexity of miscarriage etiology. Precision medicine approaches based on validated biomarkers might be necessary to identify women most likely to benefit from targeted interventions.