PDF(Pubmed)
Abstract：
UNASSIGNED: Polycystic Ovary Syndrome (PCOS) is a heritable condition with an as yet unclear etiology. Various factors, such as genetics, lifestyle, environment, inflammation, insulin resistance, hyperandrogenism, iron metabolism, and gut microbiota, have been proposed as potential contributors to PCOS. Nevertheless, a systematic assessment of modifiable risk factors and their causal effects on PCOS is lacking. This study aims to establish a comprehensive profile of modifiable risk factors for PCOS by utilizing a two-sample Mendelian Randomization (MR) framework.
UNASSIGNED: After identifying over 400 modifiable risk factors, we employed a two-sample MR approach, including the Inverse Variance Weighted (IVW) method, Weighted Median method, and MR-Egger, to investigate their causal associations with PCOS. The reliability of our estimates underwent rigorous examination through sensitivity analyses, encompassing Cochran\'s Q test, MR-Egger intercept analysis, leave-one-out analysis, and funnel plots.
UNASSIGNED: We discovered that factors such as smoking per day, smoking initiation, body mass index, basal metabolic rate, waist-to-hip ratio, whole body fat mass, trunk fat mass, overall health rating, docosahexaenoic acid (DHA) (22:6n-3) in blood, monounsaturated fatty acids, other polyunsaturated fatty acids apart from 18:2 in blood, omega-3 fatty acids, ratio of bisallylic groups to double bonds, omega-9 and saturated fatty acids, total lipids in medium VLDL, phospholipids in medium VLDL, phospholipids in very large HDL, triglycerides in very large HDL, the genus Oscillibacter, the genus Alistipes, the genus Ruminiclostridium 9, the class Mollicutes, and the phylum Tenericutes, showed a significant effect on heightening genetic susceptibility of PCOS. In contrast, factors including fasting insulin interaction with body mass index, sex hormone-binding globulin, iron, ferritin, SDF1a, college or university degree, years of schooling, household income, the genus Enterorhabdus, the family Bifidobacteriaceae, the order Bifidobacteriales, the class Actinobacteria, and the phylum Actinobacteria were determined to reduce risk of PCOS.
UNASSIGNED: This study innovatively employs the MR method to assess causal relationships between 400 modifiable risk factors and the susceptibility of PCOS risk. It supports causal links between factors like smoking, BMI, and various blood lipid levels and PCOS. These findings offer novel insights into potential strategies for the management and treatment of PCOS.
UNASSIGNED: After identifying over 400 modifiable risk factors, we employed a two-sample MR approach, including the Inverse Variance Weighted (IVW) method, Weighted Median method, and MR-Egger, to investigate their causal associations with PCOS. The reliability of our estimates underwent rigorous examination through sensitivity analyses, encompassing Cochran\'s Q test, MR-Egger intercept analysis, leave-one-out analysis, and funnel plots.
UNASSIGNED: We discovered that factors such as smoking per day, smoking initiation, body mass index, basal metabolic rate, waist-to-hip ratio, whole body fat mass, trunk fat mass, overall health rating, docosahexaenoic acid (DHA) (22:6n-3) in blood, monounsaturated fatty acids, other polyunsaturated fatty acids apart from 18:2 in blood, omega-3 fatty acids, ratio of bisallylic groups to double bonds, omega-9 and saturated fatty acids, total lipids in medium VLDL, phospholipids in medium VLDL, phospholipids in very large HDL, triglycerides in very large HDL, the genus Oscillibacter, the genus Alistipes, the genus Ruminiclostridium 9, the class Mollicutes, and the phylum Tenericutes, showed a significant effect on heightening genetic susceptibility of PCOS. In contrast, factors including fasting insulin interaction with body mass index, sex hormone-binding globulin, iron, ferritin, SDF1a, college or university degree, years of schooling, household income, the genus Enterorhabdus, the family Bifidobacteriaceae, the order Bifidobacteriales, the class Actinobacteria, and the phylum Actinobacteria were determined to reduce risk of PCOS.
UNASSIGNED: This study innovatively employs the MR method to assess causal relationships between 400 modifiable risk factors and the susceptibility of PCOS risk. It supports causal links between factors like smoking, BMI, and various blood lipid levels and PCOS. These findings offer novel insights into potential strategies for the management and treatment of PCOS.
摘要：
■多囊卵巢综合征（PCOS）是一种遗传性疾病，病因尚不清楚。各种因素,比如遗传学，生活方式,环境,炎症,胰岛素抵抗，雄激素过多症,铁代谢，和肠道微生物群，已被提议为PCOS的潜在贡献者。然而，缺乏对可改变的危险因素及其对PCOS的因果影响的系统评估.这项研究旨在通过利用两个样本的孟德尔随机化（MR）框架来建立PCOS的可修改危险因素的全面概况。
■在确定了400多个可修改的风险因素后，我们采用了双样本MR方法，包括逆方差加权(IVW)方法，加权中位数法，和MR-Egger,调查他们与PCOS的因果关系。通过敏感性分析，我们估计的可靠性经过了严格的检验，包括科克伦的Q测试，MR-Egger截距分析,遗漏分析，和漏斗图。
■我们发现每天吸烟等因素，开始吸烟,身体质量指数,基础代谢率，腰臀比,全身脂肪量,躯干脂肪量,整体健康评级，血液中的二十二碳六烯酸（DHA）（22:6n-3），单不饱和脂肪酸，除了血液中的18:2之外，其他多不饱和脂肪酸，omega-3脂肪酸，双烯丙基与双键的比率，omega-9和饱和脂肪酸，中等VLDL中的总脂质，VLDL培养基中的磷脂，非常大的HDL中的磷脂，非常大的HDL中的甘油三酯，镰刀杆菌属，Alistipes属，Ruminiclostridium9属，Mollicutes类，和Tenericutes门，对提高PCOS的遗传易感性有显著影响。相比之下,因素包括空腹胰岛素与体重指数的相互作用，性激素结合球蛋白，铁,铁蛋白,SDF1a,学院或大学学位，多年的教育，家庭收入,肠纹肌属，双歧杆菌科，双歧杆菌的订单，放线菌类，和放线菌门被确定为降低PCOS的风险。
■这项研究创新性地采用MR方法来评估400个可改变的危险因素与PCOS风险易感性之间的因果关系。它支持吸烟等因素之间的因果关系，BMI,以及各种血脂水平和PCOS。这些发现为PCOS的管理和治疗提供了新的见解。
■在确定了400多个可修改的风险因素后，我们采用了双样本MR方法，包括逆方差加权(IVW)方法，加权中位数法，和MR-Egger,调查他们与PCOS的因果关系。通过敏感性分析，我们估计的可靠性经过了严格的检验，包括科克伦的Q测试，MR-Egger截距分析,遗漏分析，和漏斗图。
■我们发现每天吸烟等因素，开始吸烟,身体质量指数,基础代谢率，腰臀比,全身脂肪量,躯干脂肪量,整体健康评级，血液中的二十二碳六烯酸（DHA）（22:6n-3），单不饱和脂肪酸，除了血液中的18:2之外，其他多不饱和脂肪酸，omega-3脂肪酸，双烯丙基与双键的比率，omega-9和饱和脂肪酸，中等VLDL中的总脂质，VLDL培养基中的磷脂，非常大的HDL中的磷脂，非常大的HDL中的甘油三酯，镰刀杆菌属，Alistipes属，Ruminiclostridium9属，Mollicutes类，和Tenericutes门，对提高PCOS的遗传易感性有显著影响。相比之下,因素包括空腹胰岛素与体重指数的相互作用，性激素结合球蛋白，铁,铁蛋白,SDF1a,学院或大学学位，多年的教育，家庭收入,肠纹肌属，双歧杆菌科，双歧杆菌的订单，放线菌类，和放线菌门被确定为降低PCOS的风险。
■这项研究创新性地采用MR方法来评估400个可改变的危险因素与PCOS风险易感性之间的因果关系。它支持吸烟等因素之间的因果关系，BMI,以及各种血脂水平和PCOS。这些发现为PCOS的管理和治疗提供了新的见解。
