Verdiesen Renée M G, von Berg Joanna, Said M Abdullah, van der Harst Pim, Mahajan Anubha, van Gils Carla H, van der Schouw Yvonne T, Onland-Moret N Charlotte
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The Netherlands.
Division Laboratory, Pharmacy and Biomedical Genetics, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
Rev Cardiovasc Med. 2022 Jul 25;23(8):269. doi: 10.31083/j.rcm2308269. eCollection 2022 Aug.
Higher age-specific circulating anti-Müllerian hormone (AMH) levels have been linked to a lower risk of cardiometabolic outcomes. However, whether AMH has a casual role in the etiology of these diseases is unknown. The objective of this study was therefore to explore if circulating AMH levels have a causal effect on risk of coronary artery disease (CAD), ischemic stroke and type 2 diabetes (T2D) in women, using a two-sample Mendelian randomization (MR) approach.
We used four single nucleotide polymorphisms (SNPs) from the most recent AMH GWAS meta-analysis as instrumental variables. Summary-level data for CAD (n = 149,752; 11,802 cases), ischemic stroke (n = 17,541; 4678 cases) and T2D (n = 464,389; 30,052 cases) were extracted from the UK Biobank, the Stroke Genetics Network, and DIAMANTE consortia, respectively. To assess the presence of potential pleiotropy we tested the association of the four AMH SNPs, both individually and combined in a weighted genetic risk score, with a range of cardiovascular risk factors and intermediate traits using UK Biobank data.
MR estimates, i.e., inverse variance-weighted odds ratios ( ), did not support a causal effect of circulating AMH levels on CAD ( = 1.13, 95% CI: 0.95-1.35), ischemic stroke ( = 1.11, 95% CI: 0.83-1.49), and T2D ( = 0.98, 95% CI: 0.87-1.10). After adjustment for multiple testing, we observed associations between genetically predicted AMH and age at menopause, and age at menarche, but not with intermediate traits on the causal pathway between AMH and cardiometabolic health, such as atherosclerosis or glucose levels.
This study does not provide evidence for a causal effect of circulating AMH levels on CAD, ischemic stroke and T2D in women, although weak instrument bias cannot be excluded.
特定年龄的循环抗苗勒管激素（AMH）水平较高与较低的心血管代谢疾病风险相关。然而，AMH在这些疾病病因中是否具有因果作用尚不清楚。因此，本研究的目的是使用两样本孟德尔随机化（MR）方法，探讨循环AMH水平对女性冠状动脉疾病（CAD）、缺血性中风和2型糖尿病（T2D）风险是否具有因果效应。
我们使用了来自最新AMH全基因组关联研究（GWAS）荟萃分析的四个单核苷酸多态性（SNP）作为工具变量。分别从英国生物银行、中风遗传学网络和DIAMANTE联盟中提取CAD（n = 149,752；11,802例）、缺血性中风（n = 17,541；4,678例）和T2D（n = 464,389；30,052例）的汇总水平数据。为了评估潜在的多效性，我们使用英国生物银行数据，分别测试了四个AMH SNP单独以及组合成加权遗传风险评分后与一系列心血管危险因素和中间性状的关联。
MR估计值，即逆方差加权比值比（ ），不支持循环AMH水平对CAD（ = 1.13，95%CI：0.95 - 1.35）、缺血性中风（ = 1.11，95%CI：0.83 - 1.49）和T2D（ = 0.98，95%CI：0.87 - 1.10）有因果效应。在进行多重检验校正后，我们观察到遗传预测的AMH与绝经年龄和初潮年龄之间存在关联，但与AMH和心血管代谢健康之间因果途径上的中间性状，如动脉粥样硬化或血糖水平无关。
本研究没有提供循环AMH水平对女性CAD、缺血性中风和T2D有因果效应的证据，尽管不能排除弱工具偏倚。
