■先前的观察性研究已确定血浆同型半胱氨酸(Hcy)水平升高与多囊卵巢综合征(PCOS)之间存在相关性。本研究旨在确定Hcy与PCOS在遗传水平上是否存在因果关系。
■进行了双样本孟德尔随机化(TSMR)研究,以评估血浆Hcy水平的遗传影响,叶酸,维生素B12和维生素B6对欧洲血统个体的PCOS。与Hcy相关的独立单核苷酸多态性(SNPs)(n=12),叶酸(n=2),维生素B12(n=10),选择全基因组显著性水平(P<5×10-8)的维生素B6(n=1)作为工具变量(IVs)。有关PCOS的数据来自Apollo数据库。因果估计的主要方法是方差逆加权(IVW),辅以敏感性分析,以验证结果。
■该研究没有发现遗传证据表明血浆Hcy水平之间存在因果关系,叶酸,维生素B12,维生素B6和PCOS。效果大小,通过随机效应IVW确定,如下:Hcy每标准偏差增加,OR=1.117,95CI:(0.842,1.483),P=0.442;叶酸每标准偏差增加,OR=1.008,CI:(0.546,1.860),P=0.981;维生素B12每标准偏差增加,OR=0.978,CI:(0.808,1.185),P=0.823;维生素B6每标准偏差增加,OR=0.967,CI:(0.925,1.012),P=0.145。每种营养素暴露和PCOS的固定效应IVW结果与随机效应IVW结果一致。额外的敏感性分析加强了这些结果。
■我们的研究结果表明,Hcy之间没有因果关系,叶酸,维生素B12,维生素B6水平,和PCOS。
UNASSIGNED: Previous observational studies have identified a correlation between elevated plasma homocysteine (Hcy) levels and polycystic ovary syndrome (PCOS). This study aimed to determine whether a causal relationship exists between Hcy and PCOS at the genetic level.
UNASSIGNED: A two-sample Mendelian Randomization (TSMR) study was implemented to assess the genetic impact of plasma levels of Hcy, folate, vitamin B12, and vitamin B6 on PCOS in individuals of European ancestry. Independent single nucleotide polymorphisms (SNPs) associated with Hcy (n=12), folate (n=2), vitamin B12 (n=10), and vitamin B6 (n=1) at genome-wide significance levels (P<5×10-8) were selected as instrumental variables (IVs). Data concerning PCOS were obtained from the Apollo database. The primary method of causal estimation was inverse variance weighting (IVW), complemented by sensitivity analyses to validate the results.
UNASSIGNED: The study found no genetic evidence to suggest a causal association between plasma levels of Hcy, folate, vitamin B12, vitamin B6, and PCOS. The effect sizes, determined through random-effect IVW, were as follows: Hcy per standard deviation increase, OR = 1.117, 95%CI: (0.842, 1.483), P = 0.442; folate per standard deviation increase, OR = 1.008, CI: (0.546, 1.860), P = 0.981; vitamin B12 per standard deviation increase, OR = 0.978, CI: (0.808, 1.185), P = 0.823; and vitamin B6 per standard deviation increase, OR = 0.967, CI: (0.925, 1.012), P = 0.145. The fixed-effect IVW results for each nutrient exposure and PCOS were consistent with the random-effect IVW findings, with additional sensitivity analyses reinforcing these outcomes.
UNASSIGNED: Our findings indicate no causal link between Hcy, folate, vitamin B12, vitamin B6 levels, and PCOS.