Table 2. Odds ratio (OR) estimates of bipolar disorder, major depressive disorder (MDD) and schizophrenia per 1-standard deviation increment in BMI based on IVW, MR-Egger and weighted median approaches.
| Included SNPsa | Parameter | Statistic | IVW | Weighted median | MR-Egger | MR-Egger (SIMEX)b |
|---|---|---|---|---|---|---|
| Outcome: Bipolar disorder | ||||||
| All | Intercept | Odds (95% CI) | — | — | 0.99 (0.97; 1.01) | 0.99 (0.97; 1.01) |
| (97 SNPs) | P | — | — | 0.281 | 0.294 | |
| OR | OR (95% CI) | 0.90 (0.69; 1.16) | 0.88 (0.62; 1.25) | 1.23 (0.65; 2.31) | 1.26 (0.63; 2.52) | |
| P | 0.416 | 0.482 | 0.517 | 0.516 | ||
| Non-influential | Intercept | Odds (95% CI) | — | — | 0.99 (0.98; 1.01) | 0.99 (0.98; 1.01) |
| (92 SNPs) | P | — | — | 0.319 | 0.335 | |
| OR | OR (95% CI) | 0.93 (0.74; 1.17) | 0.88 (0.62; 1.26) | 1.19 (0.69; 2.05) | 1.21 (0.67; 2.20) | |
| P | 0.532 | 0.487 | 0.518 | 0.526 | ||
| Outcome: Schizophrenia | ||||||
| All | Intercept | Odds (95% CI) | — | — | 0.99 (0.98; 1.00) | 0.99 (0.97; 1.00) |
| (96 SNPs) | P | — | — | 0.101 | 0.103 | |
| OR | OR (95% CI) | 0.98 (0.80; 1.19) | 0.93 (0.78; 1.11) | 1.41 (0.87; 2.27) | 1.46 (0.86; 2.47) | |
| P | 0.806 | 0.420 | 0.162 | 0.161 | ||
| Non-influential | Intercept | Odds (95% CI) | — | — | 0.99 (0.98; 1.00) | 0.99 (0.98; 1.01) |
| (92 SNPs) | P | — | — | 0.280 | 0.283 | |
| OR | OR (95% CI) | 1.01 (0.86; 1.18) | 0.93 (0.78; 1.10) | 1.22 (0.83; 1.81) | 1.25 (0.81; 1.92) | |
| P | 0.944 | 0.406 | 0.310 | 0.315 | ||
| Outcome: Major depressive disorder | ||||||
| All | Intercept | Odds (95% CI) | — | — | 1.00 (0.98; 1.01) | 1.00 (0.98; 1.01) |
| (90 SNPs) | P | — | — | 0.669 | 0.622 | |
| OR | OR (95% CI) | 1.15 (0.92; 1.44) | 1.40 (1.03; 1.90) | 1.28 (0.74; 2.24) | 1.33 (0.72; 2.47) | |
| P | 0.221 | 0.035 | 0.374 | 0.364 | ||
| Non-influential | Intercept | Odds (95% CI) | — | — | 0.99 (0.98; 1.01) | 0.99 (0.98; 1.01) |
| (86 SNPs) | P | — | — | 0.385 | 0.328 | |
| OR | OR (95% CI) | 1.25 (1.02; 1.52) | 1.45 (1.05; 1.99) | 1.52 (0.93; 2.49) | 1.60 (0.93; 2.75) | |
| P | 0.030 | 0.026 | 0.094 | 0.087 | ||
95% CI: 95% Confidence interval. P: P-value. SIMEX: Simulation Extrapolation.
aAll corresponds to Mendelian randomization analysis using all BMI-associated SNPs available in the correspondent psychiatric dataset. “Non-influential” is similar, but excludes SNPs classified as influential using statistical tests based on studentized residuals and Cook’s distance (see Materials and Methods for details).
bThis differs from regular MR-Egger regression because it uses the SIMEX method to correct for regression dilution bias.