Table 2:
Results from sIL-6R Mendelian Randomization analyses
| UK Biobank Sample | PGC MDD 2018 coefficients | ||||||
|---|---|---|---|---|---|---|---|
| Method / SNP selection | Odds ratio (95% CI) | P | # SNPs | Odds ratio (95% CI) | P | # SNPs | |
| van Dongen 2014 coefficients | Ratio of Coefficients (rs12126142) | 1.026 (1.009–1.042) | 0.002 | 1 | 1.014 (1.001–1.027) | 0.033 | 1 |
| Maximum Likelihood | |||||||
| Clumping at r2=0.001 | ** | ** | 2 | ** | ** | 2 | |
| Clumping at r2=0.01 | 1.024 (1.008–1.040) | 0.004 | 4 | 1.015 (1.002–1.027) | 0.024 | 4 | |
| GSMR | |||||||
| Clumping at r2=0.05 | 1.026 (1.010–1.043) | 0.001 | 14 | 1.015 (1.002–1.028) | 0.019 | 16 | |
| Clumping at r2=0.10 | 1.026 (1.010–1.042) | 0.001 | 23 | 1.017 (1.005–1.030) | 0.007 | 23 | |
| Clumping at r2=0.15 | 1.023 (1.007–1.038) | 0.004 | 26 | 1.016 (1.004–1.029) | 0.009 | 26 | |
| Clumping at r2=0.20 | 1.024 (1.008–1.040) | 0.002 | 28 | 1.016 (1.004–1.028) | 0.010 | 29 | |
| PCA-IVW | 1.023 (1.006–1.039) | 0.006 | 491 (4 PCs) | 1.016 (1.003–1.029) | 0.019 | 500 (4 PCs) | |
| PCA-IVW (conditional)* | 1.029 (0.994–1.065) | 0.107 | 275 (2 PCs) | 1.012 (0.985–1.040) | 0.387 | 280 (2 PCs) | |
| IMPROVE coefficients | Ratio of Coefficients (rs2228145) | 1.040 (1.014–1.066) | 0.002 | 1 | 1.021 (1.002–1.041) | 0.032 | 1 |
| Maximum Likelihood | |||||||
| Clumping at r2=0.001 | ** | ** | 2 | ** | ** | 2 | |
| Clumping at r2=0.01 | 1.045 (1.022–1.069) | < 0.001 | 4 | 1.023 (1.004–1.041) | 0.015 | 4 | |
| COJO at p=5e-8 | 1.016 (1.003–1.030) | 0.016 | 7 | 1.012 (1.001–1.023) | 0.026 | 7 | |
| COJO at p=1e-6 | 1.018 (1.005–1.032) | 0.009 | 9 | 1.013 (1.003–1.024) | 0.015 | 9 | |
| COJO at p=0.0001 | 1.013 (1.002–1.024) | 0.017 | 15 | 1.009 (1.000–1.017) | 0.040 | 14 | |
| GSMR | |||||||
| Clumping at r2=0.05 | 1.021 (1.004–1.039) | 0.016 | 11 | 1.008 (0.994–1.022) | 0.274 | 13 | |
| Clumping at r2=0.10 | 1.023 (1.006–1.040) | 0.009 | 15 | 1.008 (0.995–1.022) | 0.239 | 17 | |
| Clumping at r2=0.15 | 1.027 (1.010–1.044) | 0.002 | 22 | 1.009 (0.996–1.022) | 0.197 | 25 | |
| Clumping at r2=0.20 | 1.024 (1.008–1.041) | 0.003 | 25 | 1.012 (0.999–1.025) | 0.074 | 28 | |
| PCA-IVW | 1.023 (1.002–1.045) | 0.029 | 519 (7 PCs) | 1.021 (1.004–1.038) | 0.014 | 533 (7 PCs) | |
This analysis used coefficients from van Dongen 2014 supplementary table 3, a GWAS of sIL-6R conditional on rs2228145 genotype
Not enough SNPs to perform analysis
Table 2 shows the results of Mendelian Randomization analyses using two sIL-6R datasets (van Dongen 2014 and IMPROVE, shown on the left edge) and two outcome datasets (UK Biobank and PGC MDD 2018, shown across the top). The methods column shows both the analysis method (aligned left) and the SNP selection method (aligned right). For the Maximum Likelihood analysis, LD clumping was performed over a distance of 10,000 kilobases, and for the GSMR analysis clumping was performed using a 1 megabase window. For PCA-IVW analyses, the number appearing in parenthesis after the number of SNPs in the number of principle components (PCs) extracted from the SNP data to explain 99% of the variance.