UNASSIGNED: We conducted a two-sample bidirectional Mendelian randomization (MR) analysis using publicly available genome-wide association studies (GWAS) statistics from multiple consortia. The inverse-variance weighted (IVW) method was used for the primary analysis. We applied four complementary methods, including weighted median, weighted mode, MR-Egger regression, and Cochrane\'s Q value, to detect and correct the effects of horizontal pleiotropy.
UNASSIGNED: Genetically determined constipation (OR = 0.97, 95% CI: 0.91-1.03, P = 0.28) and diarrhea (OR = 1.00, 95% CI: 0.99-1.01, P = 0.90) did not have a causal effect on HEM but stool frequency (OR = 1.28, 95% CI: 1.05-1.55, P = 0.01), waist-to-hip ratio adjusted for BMI (OR = 1.11, 95% CI: 1.06-1.64, P = 1.59×10-5), and order Burkholderiales (OR = 1.09, 95% CI = 1.04-1.14, p = 1.63×10-4) had a causal effect on. Furthermore, we found a significant causal effect of constipation on HEM in the reverse MR analysis (OR = 1.21, 95% CI: 1.13-1.28, P = 3.72×10-9). The results of MR-Egger regression, Weighted Median, and Weighted Mode methods were consistent with those of the IVW method. Horizontal pleiotropy was unlikely to distort the causal estimates, as indicated by the sensitivity analysis.
UNASSIGNED: Our MR analysis reveals a causal association between stool frequency and waist-to-hip ratio with HEM, despite variations in results reported by observational studies. Unexpectedly, we found a relationship between the order Burkholderiales in the gut flora and HEM, although the mechanism is unclear.
■我们使用来自多个联盟的公开可用的全基因组关联研究(GWAS)统计数据进行了双样本双向孟德尔随机化(MR)分析。采用逆方差加权(IVW)方法进行初步分析。我们应用了四种互补的方法,包括加权中位数,加权模式,MR-Egger回归,和Cochrane的Q值,检测和纠正水平多效性的影响。
■遗传确定的便秘(OR=0.97,95%CI:0.91-1.03,P=0.28)和腹泻(OR=1.00,95%CI:0.99-1.01,P=0.90)对HEM没有因果关系,但对大便频率有因果关系(OR=1.28,95%CI:1.05-1.55,P=0.01),根据BMI调整腰臀比(OR=1.11,95%CI:1.06-1.64,P=1.59×10-5),和伯克霍德里亚令(OR=1.09,95%CI=1.04-1.14,p=1.63×10-4)对此外,我们在反向MR分析中发现便秘对HEM有显著的因果效应(OR=1.21,95%CI:1.13-1.28,P=3.72×10-9).MR-Egger回归的结果,加权中位数,加权模式方法与IVW方法一致。水平多效性不太可能扭曲因果估计,如敏感性分析所示。
■我们的MR分析揭示了大便频率和腰臀比与HEM之间的因果关系,尽管观察性研究报告的结果有所不同。出乎意料的是,我们发现了肠道菌群中的Burkholderiales顺序和HEM之间的关系,尽管机制尚不清楚。