Table 3. Odds ratio (OR) estimates of bipolar disorder, major depressive disorder and schizophrenia per 1- standard deviation increment in BMI based on IVW, MR-Egger and weighted median approaches, within independent subgroups of SNPs defined using biological criteria.
| Influential SNPs | SNP subgroup | Statistic | IVW | Weighted median | MR-Egger | MR-Egger (SIMEX)e |
|---|---|---|---|---|---|---|
| Outcome: Bipolar disorder | ||||||
| Includeda | Neuronalc | OR (95% CI) | 0.93 (0.66; 1.32) | 0.89 (0.59; 1.34) | 1.19 (0.54; 2.60) | 1.19 (0.51; 2.75) |
| (54 SNPs) | P | 0.684 | 0.570 | 0.662 | 0.680 | |
| Otherd | OR (95% CI) | 0.83 (0.55; 1.27) | 0.97 (0.57; 1.64) | 1.33 (0.38; 4.68) | 1.42 (0.32; 6.34) | |
| (43 SNPs) | P | 0.386 | 0.902 | 0.645 | 0.636 | |
| Excludedb | Neuronalc | OR (95% CI) | 0.94 (0.70; 1.27) | 0.89 (0.59; 1.34) | 1.09 (0.56; 2.10) | 1.09 (0.54; 2.20) |
| (50 SNPs) | P | 0.698 | 0.574 | 0.802 | 0.809 | |
| Otherd | OR (95% CI) | 0.90 (0.62; 1.32) | 0.97 (0.57; 1.66) | 1.62 (0.52; 5.02) | 1.81 (0.47; 6.97) | |
| (42 SNPs) | P | 0.597 | 0.917 | 0.394 | 0.377 | |
| Outcome: Schizophrenia | ||||||
| Includeda | Neuronalc | OR (95% CI) | 1.00 (0.80; 1.26) | 0.93 (0.76; 1.13) | 1.30 (0.77; 2.21) | 1.33 (0.75; 2.34) |
| (54 SNPs) | P | 0.992 | 0.474 | 0.317 | 0.318 | |
| Otherd | OR (95% CI) | 0.93 (0.64; 1.35) | 0.86 (0.66; 1.13) | 1.75 (0.58; 5.24) | 1.95 (0.53; 7.15) | |
| (42 SNPs) | P | 0.687 | 0.285 | 0.311 | 0.306 | |
| Excludedb | Neuronalc | OR (95% CI) | 1.06 (0.86; 1.30) | 0.93 (0.76; 1.13) | 1.15 (0.71; 1.86) | 1.17 (0.70; 1.95) |
| (52 SNPs) | P | 0.602 | 0.472 | 0.554 | 0.545 | |
| Otherd | OR (95% CI) | 0.91 (0.70; 1.20) | 0.86 (0.66; 1.12) | 1.37 (0.61; 3.09) | 1.46 (0.55; 3.88) | |
| (40 SNPs) | P | 0.495 | 0.271 | 0.442 | 0.440 | |
| Outcome: Major depressive disorder | ||||||
| Includeda | Neuronalc | OR (95% CI) | 1.16 (0.90; 1.50) | 1.44 (1.01; 2.06) | 1.26 (0.70; 2.27) | 1.29 (0.69; 2.43) |
| (54 SNPs) | P | 0.254 | 0.051 | 0.424 | 0.422 | |
| Otherd | OR (95% CI) | 1.13 (0.71; 1.80) | 1.36 (0.81; 2.28) | 1.38 (0.28; 6.70) | 1.52 (0.21; 10.83) | |
| (36 SNPs) | P | 0.594 | 0.257 | 0.680 | 0.669 | |
| Excludedb | Neuronalc | OR (95% CI) | 1.20 (0.94; 1.53) | 1.48 (1.02; 2.15) | 1.60 (0.92; 2.77) | 1.66 (0.92; 3.00) |
| (52 SNPs) | P | 0.142 | 0.042 | 0.096 | 0.089 | |
| Otherd | OR (95% CI) | 1.37 (0.95; 1.98) | 1.39 (0.82; 2.35) | 1.46 (0.43; 4.97) | 1.62 (0.36; 7.32) | |
| (34 SNPs) | P | 0.090 | 0.227 | 0.536 | 0.517 | |
95% CI: 95% Confidence interval. P: P-value. SIMEX: Simulation Extrapolation.
aSNPs classified as influential using statistical tests based on studentized residuals and Cook’s distance (see Materials and Methods for details) were included.
bSNPs classified as influential were excluded.
cIncludes SNPs belonging to “neuronal developmental processes”, “neurotransmission”, “hypothalamic expression and regulatory function” or “neuronal Expression” biological categories.
dIncludes SNPs belonging to the remaining biological categories.
eThis differs from regular MR-Egger regression because it uses the SIMEX method to correct for regression dilution bias.