Table 1.
Gut microbiota | MR Results | Heterogeneity | Horizontal pleiotropy | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Methods | SNPs | Beta | SE |
P- value |
OR (95% CI) | Cochran’s Q | I2 |
P- value |
Egger intercept |
SE |
P- value |
RSSobs |
P- value |
|
Asthma | ||||||||||||||
Barnesiella | IVW | 13 | 0.092 | 0.030 | 2.10E-03 | 1.097(1.034-1.163) | 12.410 | 3.3 | 0.413 | -0.012 | 0.008 | 0.160 | 14.429 | 0.448 |
ML | 13 | 0.096 | 0.031 | 1.71E-03 | 1.101(1.037-1.169) | 11.998 | 0 | 0.446 | ||||||
MR Egger | 13 | 0.234 | 0.098 | 3.69E-02 | 1.263(1.042-1.532) | 10.144 | 0 | 0.518 | ||||||
Weighted median | 13 | 0.078 | 0.043 | 7.00E-02 | 1.081(0.994-1.177) | |||||||||
RAPS | 13 | 0.092 | 0.030 | 2.55E-03 | 1.096(1.033-1.164) | |||||||||
MR-PRESSO | 13 | 0.092 | 0.030 | 9.61E-03 | 1.097(1.034-1.163) | |||||||||
CandidatusSoleaferrea | IVW | 7 | -0.068 | 0.028 | 1.58E-02 | 0.934(0.884-0.987) | 3.276 | 0 | 0.773 | -0.010 | 0.025 | 0.708 | 4.422 | 0.811 |
ML | 7 | -0.070 | 0.029 | 1.69E-02 | 0.933(0.881-0.988) | 3.149 | 0 | 0.790 | ||||||
MR Egger | 7 | 0.039 | 0.273 | 8.91E-01 | 1.040(0.610-1.774) | 3.119 | 0 | 0.682 | ||||||
Weighted median | 7 | -0.063 | 0.038 | 9.10E-02 | 0.938(0.872-1.010) | |||||||||
RAPS | 7 | -0.015 | 0.025 | 5.52E-01 | 0.985(0.939-1.034) | |||||||||
MR-PRESSO | 7 | -0.068 | 0.021 | 1.71E-02 | 0.934(0.897-0.973) | |||||||||
Ruminococcaceae UCG014 | IVW | 7 | 0.114 | 0.039 | 3.06E-03 | 1.121(1.039-1.210) | 5.583 | 0 | 0.472 | 0.005 | 0.009 | 0.653 | 7.279 | 0.562 |
ML | 7 | 0.118 | 0.041 | 3.68E-03 | 1.126(1.039-1.219) | 5.317 | 0 | 0.504 | ||||||
MR Egger | 7 | 0.066 | 0.110 | 5.77E-01 | 1.068(0.861-1.325) | 5.339 | 6.4 | 0.376 | ||||||
Weighted median | 7 | 0.096 | 0.052 | 6.61E-02 | 1.100(0.994-1.219) | |||||||||
RAPS | 7 | 0.089 | 0.033 | 7.43E-03 | 1.093(1.024-1.167) | |||||||||
MR-PRESSO | 7 | 0.114 | 0.037 | 2.19E-02 | 1.121(1.042-1.206) | |||||||||
Adult-onset asthma | ||||||||||||||
Akkermansia | IVW | 6 | -0.127 | 0.056 | 2.47E-02 | 0.881(0.789-0.984) | 3.119 | 0 | 0.682 | -0.009 | 0.015 | 0.602 | 4.396 | 0.704 |
ML | 6 | -0.130 | 0.058 | 2.63E-02 | 0.878(0.783-0.985) | 3.009 | 0 | 0.699 | ||||||
MR Egger | 6 | -0.037 | 0.168 | 8.36E-01 | 0.964(0.693-1.340) | 2.799 | 0 | 0.592 | ||||||
Weighted median | 6 | -0.147 | 0.072 | 4.07E-02 | 0.863(0.749-0.994) | |||||||||
RAPS | 6 | -0.130 | 0.061 | 3.39E-02 | 0.878(0.779-0.990) | |||||||||
MR-PRESSO | 6 | -0.127 | 0.045 | 3.61E-02 | 0.881(0.807-0.961) | |||||||||
Childhood-onset asthma | ||||||||||||||
Collinsella | IVW | 4 | 0.340 | 0.124 | 6.04E-03 | 1.404(1.102-1.790) | 0.130 | 0 | 0.988 | -0.001 | 0.028 | 0.981 | 0.220 | 0.989 |
ML | 4 | 0.340 | 0.129 | 8.48E-03 | 1.405(1.091-1.810) | 0.120 | 0 | 0.989 | ||||||
MR Egger | 4 | 0.350 | 0.408 | 4.81E-01 | 1.419(0.638-3.157) | 0.130 | 0 | 0.937 | ||||||
Weighted median | 4 | 0.339 | 0.150 | 2.36E-02 | 1.404(1.047-1.883) | |||||||||
RAPS | 4 | 0.357 | 0.117 | 2.19E-03 | 1.429(1.137-1.796) | |||||||||
MR-PRESSO | 4 | 0.340 | 0.026 | 9.44E-04 | 1.404(1.335-1.477) | |||||||||
RuminococcaceaeUCG014 | IVW | 7 | 0.255 | 0.099 | 1.01E-02 | 1.291(1.063-1.568) | 7.620 | 21.3 | 0.267 | 0.015 | 0.025 | 0.585 | 10.516 | 0.334 |
ML | 7 | 0.270 | 0.094 | 4.17E-03 | 1.309(1.089-1.575) | 7.196 | 16.6 | 0.303 | ||||||
MR Egger | 7 | 0.098 | 0.289 | 7.49E-01 | 1.103(0.625-1.945) | 7.135 | 29.9 | 0.211 | ||||||
Weighted median | 7 | 0.192 | 0.121 | 1.12E-01 | 1.211(0.956-1.534) | |||||||||
RAPS | 7 | 0.213 | 0.076 | 4.86E-03 | 1.237(1.067-1.435) | |||||||||
MR-PRESSO | 7 | 0.255 | 0.099 | 4.22E-02 | 1.291(1.063-1.568) | |||||||||
Moderate-severe asthma | ||||||||||||||
FamilyXIIIAD3011group | IVW | 12 | -0.378 | 0.111 | 6.93E-04 | 0.685(0.551-0.853) | 5.846 | 0 | 0.883 | -0.012 | 0.042 | 0.787 | 6.927 | 0.899 |
ML | 12 | -0.377 | 0.115 | 1.07E-03 | 0.686(0.547-0.860) | 5.599 | 0 | 0.899 | ||||||
MR Egger | 12 | -0.238 | 0.517 | 6.55E-01 | 0.788(0.286-2.171) | 5.769 | 0 | 0.834 | ||||||
Weighted median | 12 | -0.277 | 0.147 | 5.95E-02 | 0.758(0.568-1.011) | |||||||||
RAPS | 12 | -0.300 | 0.111 | 6.63E-03 | 0.741(0.596-0.920) | |||||||||
MR-PRESSO | 12 | -0.378 | 0.081 | 7.01E-04 | 0.685(0.584-0.804) | |||||||||
Eisenbergiella | IVW | 9 | 0.273 | 0.098 | 5.28E-03 | 1.314(1.084-1.591) | 10.590 | 24.5 | 0.226 | -0.094 | 0.078 | 0.265 | 13.517 | 0.29 |
ML | 9 | 0.288 | 0.090 | 1.28E-03 | 1.334(1.120-1.590) | 10.016 | 20.1 | 0.264 | ||||||
MR Egger | 9 | 1.157 | 0.736 | 1.60E-01 | 3.180 (0.752-13.450) |
8.753 | 20 | 0.271 | ||||||
Weighted median | 9 | 0.209 | 0.121 | 8.44E-02 | 1.233(0.972-1.563) | |||||||||
RAPS | 9 | 0.310 | 0.087 | 3.73E-04 | 1.363(1.149-1.617) | |||||||||
MR-PRESSO | 9 | 0.273 | 0.098 | 2.36E-02 | 1.314(1.084-1.591) | |||||||||
Ruminiclostridium6 | IVW | 15 | -0.248 | 0.091 | 6.71E-03 | 0.780(0.652-0.934) | 11.048 | 0 | 0.682 | -0.008 | 0.020 | 0.687 | 12.764 | 0.688 |
ML | 15 | -0.246 | 0.094 | 9.17E-03 | 0.782(0.650-0.941) | 10.884 | 0 | 0.695 | ||||||
MR Egger | 15 | -0.164 | 0.224 | 4.77E-01 | 0.849(0.548-1.316) | 10.878 | 0 | 0.621 | ||||||
Weighted median | 15 | -0.116 | 0.126 | 3.57E-01 | 0.890(0.696-1.140) | |||||||||
RAPS | 15 | -0.258 | 0.098 | 8.62E-03 | 0.773(0.637-0.937) | |||||||||
MR-PRESSO | 15 | -0.248 | 0.081 | 8.62E-03 | 0.780(0.665-0.915) |
Note: Estimates with 95% CI are expressed as odds ratios for asthma, and its phenotypes in genetically predicted gut microbiota. The Cochran Q-test was used to assess the heterogeneity between the SNP-specific estimates, MR-Egger regression, and MR-PRESSO to test for evidence of pleiotropy.
Abbreviations: MR, Mendelian Randomization; SNP, single-nucleotide polymorphism; SE, Standard error; OR, Odds ratios; CI, Confidence interval; df, Degree of freedom; SE, Standard error; RSSobs, observed residual sum of squares; IVW: Inverse variance weighting; ML: Maximum likelihood; RAPS, Robust Adjusted Profile Score; MR-PRESSO, Mendelian Randomization Pleiotropy RESidual Sum and Outlier.