Table 2.
Causal effects on AUD (MVP+PGC) by MR.
| Exposure (#instruments) | Ref | IVW [27] | Weighted median [28] | MR-Egger [29] | MR-Egger intercept p | MR-PRESSO [30] | GSMR [31] | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| β (se) | p | β (se) | p | β (se) | p | #outlier | β (se) | p | #HEIDI-outlier | β (se) | p | |||
| DrnkWk (58) | [9] | 0.89 (0.06) | 1.80×10−46 | 0.89 (0.08) | 2.89×10−26 | 0.91 (0.20) | 3.80×10−6 | 0.898 | 0 | 0.89 (0.06) | 1.58×10−20 | 2 | 0.92 (0.05) | 6.37×10−79 |
| Ever smoked regularly (199) | [9] | 0.32 (0.02) | 8.72×10−51 | 0.33 (0.02) | 4.20×10−43 | 0.26 (0.08) | 1.21×10−3 | 0.471 | 3 | 0.33 (0.02) | 1.34×10−37 | 6 | 0.34 (0.01) | 1.84×10–115 |
| Current vs former smoker (12) | [9] | 0.04 (0.09) | 0.678 | 0.00 (0.06) | 0.978 | −0.33 (0.22) | 0.140 | 0.078 | 5 | 0.02 (0.04) | 0.692 | 0 | 0.04 (0.03) | 0.292 |
| Cigarettes per day (33) | [9] | 0.04 (0.06) | 0.475 | −0.10 (0.04) | 0.010 | −0.18 (0.09) | 0.034 | 1.27×10−3 | 5 | 0.09 (0.06) | 0.151 | 4 | 0.01 (0.03) | 0.643 |
| MDD (78) | [32] | 0.14 (0.03) | 8.42×10−6 | 0.14 (0.03) | 2.79×10−6 | −0.17 (0.20) | 0.390 | 0.113 | 5 | 0.14 (0.03) | 3.73×10−6 | 1 | 0.15 (0.02) | 1.65×10−18 |
| Schizophrenia (110) | [33] | 0.04 (0.01) | 2.47×10−6 | 0.04 (0.01) | 4.96×10−6 | −0.05 (0.04) | 0.202 | 0.016 | 4 | 0.04 (0.01) | 6.03×10−8 | 5 | 0.06 (0.01) | 4.65×10−26 |
| Bipolar disorder (23) | [34] | 0.03 (0.01) | 0.012 | 0.03 (0.02) | 0.049 | −0.05 (0.07) | 0.423 | 0.120 | 0 | 0.03 (0.01) | 0.020 | 0 | 0.03 (0.01) | 6.56×10−3 |
| Depressed affect sub-cluster (56) | [35] | 0.19 (0.06) | 1.75×10−3 | 0.24 (0.05) | 5.44×10−6 | −0.20 (0.28) | 0.462 | 0.147 | 7 | 0.23 (0.04) | 1.12×10−6 | 5 | 0.26 (0.04) | 6.80×10−13 |
| Neuroticism (131) | [35] | 0.20 (0.04) | 1.10×10−7 | 0.20 (0.04) | 1.10×10−7 | −0.26 (0.16) | 0.097 | 2.64×10−3 | 6 | 0.19 (0.03) | 5.83×10−8 | 4 | 0.17 (0.02) | 3.44×10−12 |
| Worry sub-cluster (61) | [35] | 0.13 (0.06) | 0.020 | 0.17 (0.05) | 8.06×10−4 | 0.04 (0.26) | 0.890 | 0.702 | 7 | 0.19 (0.04) | 8.64×10−5 | 5 | 0.21 (0.03) | 7.40×10−11 |
| Number of sexual partners (64) | [36] | 0.31 (0.04) | 3.27×10−12 | 0.36 (0.05) | 9.00×10−16 | 0.51 (0.20) | 0.011 | 0.309 | 4 | 0.33 (0.04) | 1.14×10−12 | 3 | 0.34 (0.03) | 6.13×10−28 |
| General risk tolerance (64) | [36] | 0.26 (0.06) | 7.37×10−6 | 0.28 (0.07) | 5.93×10−5 | 0.88 (0.25) | 3.69×10−4 | 9.62×10−3 | 0 | 0.26 (0.06) | 3.18×10−5 | 0 | 0.28 (0.05) | 1.91×10−9 |
| Insomnia (159) | [37] | 0.05 (0.01) | 1.90×10−5 | 0.03 (0.01) | 5.31×10−3 | −0.00 (0.05) | 0.993 | 0.288 | 7 | 0.04 (0.01) | 3.89×10−4 | 8 | 0.04 (0.01) | 3.51×10−6 |
| Cognitive performance (134) | [38] | −0.08 (0.02) | 1.03×10−3 | −0.05 (0.03) | 0.044 | −0.21 (0.12) | 0.086 | 0.282 | 4 | −0.08 (0.02) | 4.21×10−3 | 3 | −0.09 (0.02) | 6.20×10−8 |
| Educational attainment (570) | [38] | −0.22 (0.02) | 1.32×10−25 | −0.21 (0.02) | 1.45×10−17 | −0.24 (0.08) | 2.21×10−3 | 0.781 | 4 | −0.21 (0.02) | 1.37×10−23 | 16 | −0.23 (0.02) | 1.69×10−51 |
P-values labeled in bold are significant after multiple testing correction (p < 1.32×10−3). Traits labeled in bold are those having a causal effect on AUD by at least one method and consistent for the direction of effect by all 5 methods. IVW: inverse-variance weighted (IVW) linear regression. #outlier: number of pleiotropic variants which are removed from the MR estimate. #HEIDI-outlier: number of pleiotropic variants which are removed from the MR estimate. DrnkWk: drinks per week. MDD: major depressive disorder.
Depressed affect sub-cluster: depressed affect sub-cluster of neuroticism. Worry sub-cluster: worry sub-cluster of neuroticism.
Outliers are variants showing evidence of horizontal pleiotropy, which were removed before the causal estimate was made.