Genetically Determined Reproductive Aging and Coronary Heart Disease: A Bidirectional 2-sample Mendelian Randomization.

Genetically Determined Reproductive Aging and Coronary Heart Disease: A Bidirectional 2-sample Mendelian Randomization.
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遗传决定的生殖衰老与冠心病:一项双向两样本孟德尔随机化研究

DOI:
10.1210/clinem/dgac171
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发表时间:
2022-06-16
影响因子:
5.8
通讯作者:
van der Schouw, Yvonne T.
van der Schouw, Yvonne T.
中科院分区:
医学2区
文献类型:
--
作者:
Dam, Veerle;Onland-Moret, N. Charlotte;Burgess, Stephen;Chirlaque, Maria-Dolores;Peters, Sanne A. E.;Schuit, Ewoud;Tikk, Kaja;Weiderpass, Elisabete;Oliver-Williams, Clare;Wood, Angela M.;Tjonneland, Anne;Dahm, Christina C.;Overvad, Kim;Boutron-Ruault, Marie-Christine;Schulze, Matthias B.;Trichopoulou, Antonia;Ferrari, Pietro;Masala, Giovanna;Krogh, Vittorio;Tumino, Rosario;Matullo, Giuseppe;Panico, Salvatore;Boer, Jolanda M. A.;Verschuren, W. M. Monique;Waaseth, Marit;Sanchez Perez, Maria Jose;Amiano, Pilar;Imaz, Liher;Moreno-Iribas, Conchi;Melander, Olle;Harlid, Sophia;Nordendahl, Maria;Wennberg, Patrik;Key, Timothy J.;Riboli, Elio;Santiuste, Carmen;Kaaks, Rudolf;Katzke, Verena;Langenberg, Claudia;Wareham, Nicholas J.;Schunkert, Heribert;Erdmann, Jeanette;Willenborg, Christina;Hengstenberg, Christian;Kleber, Marcus E.;Delgado, Graciela;Marz, Winfried;Kanoni, Stavroula;Dedoussis, George;Deloukas, Panos;Nikpay, Majid;McPherson, Ruth;Scholz, Markus;Teren, Andrej;Butterworth, Adam S.;van der Schouw, Yvonne T.

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在观察性研究中,自然绝经早的女性生殖老化加速与冠心病(CHD)风险增加相关。相反,不利的CHD风险特征被认为会加速绝经。采用双向孟德尔随机化(MR)方法,使用自然绝经年龄(ANM)遗传变异作为遗传决定的女性生殖衰老指标,研究生殖衰老与(非)致死性CHD和CHD风险因素之间因果关系的方向和证据。我们还研究了这些变异与男性冠心病风险(因素)的关联。双样本MR,使用队列数据和汇总统计量,采用4种方法:简单和加权中位数、标准逆方差加权(IVW)回归和MR-Egger回归。将来自EPIC-CVD的数据和来自UK Biobank和公开可用的全基因组关联研究的汇总统计数据合并用于不同的分析。CHD、CHD危险因素和ANM。在不同的MR方法中,没有发现遗传决定的生殖年龄与女性CHD风险(相对风险估计值IVW = 0.99; 95%置信区间(CI),0.97-1.01)或任何CHD风险因素之间存在关联。  同样,在男性中也没有发现相关性。反向分析也没有显示CHD(危险因素)和生殖老化之间存在关联的证据。遗传决定的生殖年龄与女性CHD风险(因素)没有因果关系,男性的遗传变异也没有相关性。我们没有发现证据表明,在女性和男性的合并样本中存在反向关联。
Accelerated reproductive aging, in women indicated by early natural menopause, is associated with increased coronary heart disease (CHD) risk in observational studies. Conversely, an adverse CHD risk profile has been suggested to accelerate menopause. To study the direction and evidence for causality of the relationship between reproductive aging and (non-)fatal CHD and CHD risk factors in a bidirectional Mendelian randomization (MR) approach, using age at natural menopause (ANM) genetic variants as a measure for genetically determined reproductive aging in women. We also studied the association of these variants with CHD risk (factors) in men. Two-sample MR, using both cohort data as well as summary statistics, with 4 methods: simple and weighted median-based, standard inverse-variance weighted (IVW) regression, and MR-Egger regression. Data from EPIC-CVD and summary statistics from UK Biobank and publicly available genome-wide association studies were pooled for the different analyses. CHD, CHD risk factors, and ANM. Across different methods of MR, no association was found between genetically determined reproductive aging and CHD risk in women (relative risk estimateIVW = 0.99; 95% confidence interval (CI), 0.97-1.01), or any of the CHD risk factors. Similarly, no associations were found in men. Neither did the reversed analyses show evidence for an association between CHD (risk factors) and reproductive aging. Genetically determined reproductive aging is not causally associated with CHD risk (factors) in women, nor were the genetic variants associated in men. We found no evidence for a reverse association in a combined sample of women and men.
DOI: 10.1002/gepi.21965
发表时间: 2016-05
影响因子: 2.1
作者:
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发表时间: 2017-06-13
期刊: Circulation
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发表时间: 2009-12-15
影响因子: 24
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发表时间: 2011-09-11
期刊: NATURE
影响因子: 64.8
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通讯作者: Johnson, Toby
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DOI: 10.1038/ng.520
发表时间: 2010-02
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影响因子: 30.8
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