PDF(Pubmed)
Abstract：
The contribution of gut microbiota to the pathogenesis of polycystic ovary syndrome (PCOS) is controversial. The causal relationship to this question is worth an in-depth comprehensive of known single nucleotide polymorphisms associated with gut microbiota.
We conducted bidirectional Mendelian randomization (MR) utilizing instrumental variables associated with gut microbiota (N = 18,340) from MiBioGen GWAS to assess their impact on PCOS risk in the FinnGen GWAS (27,943 PCOS cases and 162,936 controls). Two-sample MR using inverse variance weighting (IVW) was undertaken, followed by the weighted median, weighted mode, and MR-Egger regression. In a subsample, we replicated our findings using the meta-analysis PCOS consortium (10,074 cases and 103,164 controls) from European ancestry.
IVWMR results suggested that six gut microbiota were causally associated with PCOS features. After adjusting BMI, SHBG, fasting insulin, testosterone, and alcohol intake frequency, the effect sizes were significantly reduced. Reverse MR analysis revealed that the effects of PCOS features on 13 gut microbiota no longer remained significant after sensitivity analysis and Bonferroni corrections. MR replication analysis was consistent and the results suggest that gut microbiota was likely not an independent cause of PCOS.
Our findings did not support the causal relationships between the gut microbiota and PCOS features at the genetic level. More comprehensive genome-wide association studies of the gut microbiota and PCOS are warranted to confirm their genetic relationship.
This study contains 3533 words, 0 tables, and six figures in the text as well as night supplementary files and 0 supplementary figures in the Supplementary material.
We conducted bidirectional Mendelian randomization (MR) utilizing instrumental variables associated with gut microbiota (N = 18,340) from MiBioGen GWAS to assess their impact on PCOS risk in the FinnGen GWAS (27,943 PCOS cases and 162,936 controls). Two-sample MR using inverse variance weighting (IVW) was undertaken, followed by the weighted median, weighted mode, and MR-Egger regression. In a subsample, we replicated our findings using the meta-analysis PCOS consortium (10,074 cases and 103,164 controls) from European ancestry.
IVWMR results suggested that six gut microbiota were causally associated with PCOS features. After adjusting BMI, SHBG, fasting insulin, testosterone, and alcohol intake frequency, the effect sizes were significantly reduced. Reverse MR analysis revealed that the effects of PCOS features on 13 gut microbiota no longer remained significant after sensitivity analysis and Bonferroni corrections. MR replication analysis was consistent and the results suggest that gut microbiota was likely not an independent cause of PCOS.
Our findings did not support the causal relationships between the gut microbiota and PCOS features at the genetic level. More comprehensive genome-wide association studies of the gut microbiota and PCOS are warranted to confirm their genetic relationship.
This study contains 3533 words, 0 tables, and six figures in the text as well as night supplementary files and 0 supplementary figures in the Supplementary material.
摘要：
■肠道菌群在多囊卵巢综合征（PCOS）发病机制中的作用存在争议。这个问题的因果关系值得深入综合与肠道微生物群相关的已知单核苷酸多态性。
■我们利用来自MiBioGenGWAS的与肠道微生物群相关的工具变量（N=18,340）进行了双向孟德尔随机化（MR），以评估其对FinnGenGWAS中PCOS风险的影响（27,943例PCOS病例和162,936例对照）。采用方差逆加权(IVW)进行双样本MR，其次是加权中位数，加权模式，和MR-Egger回归。在子样本中，我们使用来自欧洲血统的PCOS联盟(10,074例病例和103,164例对照)进行荟萃分析,重复了我们的发现.
■IVWMR结果表明，6种肠道菌群与PCOS特征有因果关系。调整BMI后，SHBG,空腹胰岛素，睾丸激素，和酒精摄入频率，效应大小显著减少。反向MR分析显示，经过敏感性分析和Bonferroni校正后，PCOS特征对13种肠道微生物群的影响不再显着。MR复制分析是一致的，结果表明肠道微生物群可能不是PCOS的独立原因。
■我们的研究结果不支持肠道微生物群与PCOS特征在遗传水平上的因果关系。需要对肠道菌群和PCOS进行更全面的全基因组关联研究，以确认它们的遗传关系。
■这项研究包含3533个单词，0表,文本中的六个数字以及夜间补充文件和补充材料中的0个补充数字。
■我们利用来自MiBioGenGWAS的与肠道微生物群相关的工具变量（N=18,340）进行了双向孟德尔随机化（MR），以评估其对FinnGenGWAS中PCOS风险的影响（27,943例PCOS病例和162,936例对照）。采用方差逆加权(IVW)进行双样本MR，其次是加权中位数，加权模式，和MR-Egger回归。在子样本中，我们使用来自欧洲血统的PCOS联盟(10,074例病例和103,164例对照)进行荟萃分析,重复了我们的发现.
■IVWMR结果表明，6种肠道菌群与PCOS特征有因果关系。调整BMI后，SHBG,空腹胰岛素，睾丸激素，和酒精摄入频率，效应大小显著减少。反向MR分析显示，经过敏感性分析和Bonferroni校正后，PCOS特征对13种肠道微生物群的影响不再显着。MR复制分析是一致的，结果表明肠道微生物群可能不是PCOS的独立原因。
■我们的研究结果不支持肠道微生物群与PCOS特征在遗传水平上的因果关系。需要对肠道菌群和PCOS进行更全面的全基因组关联研究，以确认它们的遗传关系。
■这项研究包含3533个单词，0表,文本中的六个数字以及夜间补充文件和补充材料中的0个补充数字。
