Table 1.
Bidirectional Mendelian Randomization Analysis
| Exposure | Outcome | Method | N SNPs | Estimate | OR | SE | P | PFDR |
|---|---|---|---|---|---|---|---|---|
| LCU | SCZ | Inverse variance weighted | 4 | β= 0.16 | 1.17 | 0.14 | 0.23 | 3.13e-1 |
| MR Egger | 4 | β= −0.96 | 0.38 | 0.88 | 0.39 | 4.74e-1 | ||
| Weighted Median | 4 | β= 0.23 | 1.26 | 0.11 | 0.03 | 5.37e-2 | ||
| MR-PRESSO (raw) | 4 | β= 0.16 | 1.17 | 0.14 | 0.32 | 4.18e-1 | ||
| CAUSE | 6236335 | γ= 0.05 | 1.05 | 0.05 | 0.61 | 6.48e-1 | ||
|
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| LCU | BIP | Inverse variance weighted | 4 | β= 0.37 | 1.45 | 0.13 | 5.37e-3 | 1.22e-2 |
| MR Egger | 4 | β= −0.63 | 0.53 | 0.90 | 0.55 | 6.23e-1 | ||
| Weighted Median | 4 | β= 0.40 | 1.49 | 0.11 | 1.78e-4 | 6.72e-4 | ||
| MR-PRESSO (raw) | 4 | β= 0.37 | 1.45 | 0.13 | 0.07 | 1.19e-1 | ||
| CAUSE | 6994919 | γ= 0.06 | 1.03 | 0.05 | 0.52 | 6.10e-1 | ||
|
| ||||||||
| CUD | SCZ | Inverse variance weighted | 2 | β= 0.45 | 1.57 | 0.13 | 6.40e-4 | 1.98e-3 |
| MR Egger | 2 | NA | NA | NA | NA | NA | ||
| Weighted Median | 2 | NA | NA | NA | NA | NA | ||
| MR-PRESSO (raw) | 2 | NA | NA | NA | NA | NA | ||
| CAUSE | 6006946 | γ= 0.05 | 1.05 | 0.05 | 0.60 | 6.48e-1 | ||
|
| ||||||||
| CUD | BIP | Inverse variance weighted | 2 | β= 0.03 | 1.03 | 0.10 | 0.79 | 8.14e-1 |
| MR Egger | 2 | NA | NA | NA | NA | NA | ||
| Weighted Median | 2 | NA | NA | NA | NA | NA | ||
| MR-PRESSO (raw) | 2 | NA | NA | NA | NA | NA | ||
| CAUSE | 6358021 | γ= 0.05 | 1.05 | 0.04 | 0.38 | 4.74e-1 | ||
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| SCZ | LCU | Inverse variance weighted | 128 | β= 0.09 | 1.09 | 0.02 | 7.45e-6 | 5.07e-5 |
| MR Egger | 128 | β= −0.02 | 0.98 | 0.09 | 8.45e-1 | 8.45e-1 | ||
| Weighted Median | 128 | β= 0.11 | 1.12 | 0.02 | 9.69e-6 | 5.49e-5 | ||
| MR-PRESSO (corrected) | 124 | β= 0.10 | 1.11 | 0.02 | 4.06e-7 | 3.45e-6 | ||
| CAUSE | 6236335 | γ= 0.05 | 1.05 | 0.01 | 9.90e-3 | 2.10e-2 | ||
|
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| SCZ | CUD | Inverse variance weighted | 129 | β= 0.21 | 1.23 | 0.03 | 3.50e-12 | 1.19e-10 |
| MR Egger | 129 | β= 0.36 | 1.43 | 0.12 | 4.02e-03 | 1.05e-2 | ||
| Weighted Median | 129 | β= 0.21 | 1.23 | 0.04 | 4.97e-08 | 5.63e-7 | ||
| MR-PRESSO (corrected) | 126 | β= 0.20 | 1.23 | 0.03 | 9.66e-12 | 1.64e-10 | ||
| CAUSE | 6006946 | γ= 0.09 | 1.09 | 0.02 | 0.02 | 3.78e-02 | ||
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| BIP | LCU | Inverse variance weighted | 36 | β= 0.11 | 1.12 | 0.03 | 1.21e-4 | 5.14e-4 |
| MR Egger | 36 | β= 0.69 | 1.99 | 0.15 | 7.90e-5 | 3.84e-4 | ||
| Weighted Median | 36 | β= 0.12 | 1.13 | 0.04 | 1.91e-3 | 5.41e-3 | ||
| MR-PRESSO (raw) | 36 | β= 0.11 | 1.12 | 0.03 | 4.89e-4 | 1.66e-3 | ||
| CAUSE | 6994919 | γ= 0.07 | 1.07 | 0.02 | 4.60e-3 | 1.12e-2 | ||
|
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| BIP | CUD | Inverse variance weighted | 38 | β= 0.06 | 1.06 | 0.05 | 0.18 | 2.66e-1 |
| MR Egger | 38 | β= 0.61 | 1.84 | 0.26 | 0.02 | 3.78e-2 | ||
| Weighted Median | 38 | β= 0.10 | 1.11 | 0.07 | 0.13 | 2.01e-1 | ||
| MR-PRESSO (raw) | 38 | β= 0.06 | 1.06 | 0.05 | 0.19 | 2.69e-1 | ||
| CAUSE | 6358021 | γ= 0.06 | 1.06 | 0.03 | 0.12 | 1.94e-1 | ||
Note: MR-PRESSO produces the same estimates as the inverse variance weighted method when no outlier SNP estimates are detected [i.e., MR-PRESSO (raw)]. When outliers are detected, those SNPs are removed, and the inverse variance weighted estimate is re-calculated [MR-PRESSO (corrected)]. NA (not applicable) is used when the particular MR method was unable to estimate the causal effect using so few SNPs. CAUSE uses the full set of overlapping SNPs between two genome-wide association studies to estimate the causal effect. The causal effect presented is the gamma (γ) estimate from the causal model and the p-value is from a test of whether the causal model is a better fit. LCU: Lifetime cannabis use; CUD: Cannabis use disorder; SCZ: Schizophrenia, BIP: Bipolar disorder; MR: Mendelian Randomization; N SNPs: number of single nucleotide polymorphisms (genetic variants) included in the analysis; OR: Odds Ratio: SE: Standard error; p: P-value; PFDR: P-value after the Benjamini-Hochberg correction.