Age at Natural Menopause and Blood Pressure Traits: Mendelian Randomization Study.
Age at Natural Menopause and Blood Pressure Traits: Mendelian Randomization Study.
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DOI：
10.3390/jcm10194299
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发表时间：
2021-09-22
影响因子：
3.9
通讯作者：
Muka T
中科院分区：
文献类型：
--
作者：
Roa-Díaz ZM;Asllanaj E;Amin HA;Rojas LZ;Nano J;Ikram MA;Drenos F;Franco OH;Pazoki R;Marques-Vidal P;Voortman T;Muka T
观察性研究表明，绝经期提前与高血压风险增加有关。这种关联是否是因果关系或由于残留混杂和/或反向因果关系仍不确定。我们的目的是评估高加索妇女自然绝经年龄（ANM）和血压特征之间的观察和因果关系。在CoLaus和鹿特丹研究的4451名绝经后妇女中进行了一项横断面和单样本孟德尔随机化（MR）研究。利用观察数据建立回归模型，研究ANM与收缩压、舒张压（SBP/DBP）和高血压的关系。单样本MR分析通过计算先前在ANM全基因组关联研究（GWAS）中鉴定的54个ANM相关变异的遗传风险评分来进行。在双样本MR分析中，我们使用来自ANM-GWAS的估计值和来自英国生物库的168，575名女性的关联估计值来评估ANM相关变异及其与SBP和DBP的因果关系。两个队列的汇总分析显示，绝经开始延迟一年与高血压风险增加2%（95%CI 0; 4）相关，绝经早期与较低的DBP相关（β = −1.31，95%CI −2.43; −0.18）。虽然单样本MR未显示ANM与血压性状之间的因果关系，但双样本MR显示ANM与SBP之间存在正因果关系;后者由DNA损伤修复相关基因驱动。目前的研究并不支持绝经早期与高血压相关的假设。我们的研究结果表明，不同的ANM相关遗传途径可能会对血压产生不同的影响。
Observational studies suggest that early onset of menopause is associated with increased risk of hypertension. Whether this association is causal or due to residual confounding and/or reverse causation remains undetermined. We aimed to evaluate the observational and causal association between age at natural menopause (ANM) and blood pressure traits in Caucasian women. A cross-sectional and one-sample Mendelian randomization (MR) study was conducted in 4451 postmenopausal women from the CoLaus and Rotterdam studies. Regression models were built with observational data to study the associations of ANM with systolic and diastolic blood pressure (SBP/DBP) and hypertension. One-sample MR analysis was performed by calculating a genetic risk score of 54 ANM-related variants, previously identified in a genome-wide association study (GWAS) on ANM. In the two-sample MR analysis we used the estimates from the ANM-GWAS and association estimates from 168,575 women of the UK Biobank to evaluate ANM-related variants and their causal association with SBP and DBP. Pooled analysis from both cohorts showed that a one-year delay in menopause onset was associated with 2% (95% CI 0; 4) increased odds of having hypertension, and that early menopause was associated with lower DBP (β = −1.31, 95% CI −2.43; −0.18). While one-sample MR did not show a causal association between ANM and blood pressure traits, the two-sample MR showed a positive causal association of ANM with SBP; the last was driven by genes related to DNA damage repair. The present study does not support the hypothesis that early onset of menopause is associated with higher blood pressure. Our results suggest different ANM-related genetic pathways could differently impact blood pressure.
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COLAUS研究：一项基于人群的研究，旨在研究心血管危险因素和代谢综合征的流行病学和遗传决定因素。
影响因子：
2.1
作者：
Firmann, Mathieu;Mayor, Vladimir;Vidal, Pedro Marques;Bochud, Murielle;Pecoud, Alain;Hayoz, Daniel;Paccaud, Fred;Preisig, Martin;Song, Kijoung S.;Yuan, Xin;Danoff, Theodore M.;Stirnadel, Heide A.;Waterworth, Dawn;Mooser, Vincent;Waeber, Gerard;Vollenweider, Peter
通讯作者：
Vollenweider, Peter
影响因子：
30.8
作者：
Das, Sayantan;Forer, Lukas;Schoenherr, Sebastian;Sidore, Carlo;Locke, Adam E.;Kwong, Alan;Vrieze, Scott I.;Chew, Emily Y.;Levy, Shawn;McGue, Matt;Schlessinger, David;Stambolian, Dwight;Loh, Po-Ru;Iacono, William G.;Swaroop, Anand;Scott, Laura J.;Cucca, Francesco;Kronenberg, Florian;Boehnke, Michael;Abecasis, Goncalo R.;Fuchsberger, Christian
通讯作者：
Fuchsberger, Christian
影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
影响因子：
4.9
作者：
El Khoudary, Samar R.
通讯作者：
El Khoudary, Samar R.
影响因子：
2.9
作者：
Kim, Jong Hae
通讯作者：
Kim, Jong Hae