PDF(Pubmed)
Abstract：
UNASSIGNED: The association between bone morphogenetic protein 10 (BMP10) and atrial fibrillation (AF) has been widely investigated by observational studies, but their causal relationships remain inconclusive. Here, we aimed to evaluate the causal effect of BMP10 on the risk of AF through single-nucleotide polymorphisms.
UNASSIGNED: A Mendelian randomization (MR) analytic framework was applied to data from two BMP10-specific genome-wide association studies comprising a total of 11,036,163 single-nucleotide polymorphisms of European ancestry. Instrument genetic variants associated with BMP10 were selected. A total of 12 AF-specific genome-wide association studies comprising a total of 5,095,117 European participants were included. Summary statistic-based methods of inverse variance weighted, MR Egger, weighted median, simple mode, and weighted mode methods were used. Pleiotropy and sensitivity were assessed.
UNASSIGNED: Specific to AF-specific genome-wide association studies, we found that BMP10 was not associated with AF among different methods (all P > 0.05). We further identified no significant horizontal pleiotropy (all P > 0.05) and no fundamental impact among various data.
UNASSIGNED: This large-scale population study upon data from BMP10- and AF-specific genome-wide association studies and a longitudinal biobank cohort indicates plausible non-causal associations between BMP10 and AF in the European populations. Further studies regarding ancestral diversity are warranted to validate such causal associations.
UNASSIGNED: A Mendelian randomization (MR) analytic framework was applied to data from two BMP10-specific genome-wide association studies comprising a total of 11,036,163 single-nucleotide polymorphisms of European ancestry. Instrument genetic variants associated with BMP10 were selected. A total of 12 AF-specific genome-wide association studies comprising a total of 5,095,117 European participants were included. Summary statistic-based methods of inverse variance weighted, MR Egger, weighted median, simple mode, and weighted mode methods were used. Pleiotropy and sensitivity were assessed.
UNASSIGNED: Specific to AF-specific genome-wide association studies, we found that BMP10 was not associated with AF among different methods (all P > 0.05). We further identified no significant horizontal pleiotropy (all P > 0.05) and no fundamental impact among various data.
UNASSIGNED: This large-scale population study upon data from BMP10- and AF-specific genome-wide association studies and a longitudinal biobank cohort indicates plausible non-causal associations between BMP10 and AF in the European populations. Further studies regarding ancestral diversity are warranted to validate such causal associations.
摘要：
■骨形态发生蛋白10（BMP10）和心房颤动（AF）之间的关联已被广泛的观察研究，但是他们的因果关系仍然没有定论。这里,我们旨在通过单核苷酸多态性评估BMP10对房颤风险的因果效应.
■孟德尔随机化（MR）分析框架应用于来自两个BMP10特异性全基因组关联研究的数据，包括总共11,036,163个欧洲血统的单核苷酸多态性。选择与BMP10相关的仪器遗传变异。包括总共5,095,117名欧洲参与者在内的总共12项AF特异性全基因组关联研究。基于统计量的逆方差加权方法总结，Egger先生,加权中位数，简单模式，并使用加权模式方法。评估了多效性和敏感性。
■特定于房颤特异性全基因组关联研究，我们发现BMP10在不同方法中与AF无关（均P>0.05）。我们进一步确定在各种数据中没有显著的水平多效性(所有P>0.05)并且没有根本影响。
■这项基于BMP10和AF特异性全基因组关联研究和纵向生物库队列数据的大规模人群研究表明，在欧洲人群中，BMP10和AF之间存在似是而非因果关联。关于祖先多样性的进一步研究需要验证这种因果关系。
■孟德尔随机化（MR）分析框架应用于来自两个BMP10特异性全基因组关联研究的数据，包括总共11,036,163个欧洲血统的单核苷酸多态性。选择与BMP10相关的仪器遗传变异。包括总共5,095,117名欧洲参与者在内的总共12项AF特异性全基因组关联研究。基于统计量的逆方差加权方法总结，Egger先生,加权中位数，简单模式，并使用加权模式方法。评估了多效性和敏感性。
■特定于房颤特异性全基因组关联研究，我们发现BMP10在不同方法中与AF无关（均P>0.05）。我们进一步确定在各种数据中没有显著的水平多效性(所有P>0.05)并且没有根本影响。
■这项基于BMP10和AF特异性全基因组关联研究和纵向生物库队列数据的大规模人群研究表明，在欧洲人群中，BMP10和AF之间存在似是而非因果关联。关于祖先多样性的进一步研究需要验证这种因果关系。
