Table 3.
Mendelian randomization estimates for the causal effect of chronic back pain (CBP) on risk factors
| IVW analysis | CAUSE analysis | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Outcome | Analysis type | # of SNPs | Beta | SE | p-value | # of SNPs | Gamma | p-value | ORf | Criterion 1a | Criterion 2b | Criterion 3c |
| Years of schooling | Primary | 21 | −0.145 | 0.043 | 6.87E-04 | 611 | −0.126 | 2.97E-06 | 0.86(0.80,0.94) | Yes | Yes | No |
| Sensitivityd | 0 | - | - | - | 292 | −0.081 | 1.09E-02 | - | ||||
| Ever smokere | Primary | 21 | 0.191 | 0.067 | 4.53E-03 | 609 | 0.243 | 1.79E-05 | 1.21(1.06,1.38) | Yes | Yes | Yes |
| Sensitivityd | 1 | 0.015 | 0.134 | 9.09E-01 | 263 | 0.121 | 6.78E-02 | 1.02(0.78,1.32) | ||||
| Alcohol intake frequency | Primary | 21 | 0.178 | 0.048 | 2.16E-04 | 609 | 0.124 | 2.05E-04 | 1.19(1.09,1.31) | Yes | Yes | Yes |
| Sensitivityd | 3 | 0.055 | 0.050 | 2.72E-01 | 259 | 0.083 | 6.13E-02 | 1.06(0.96,1.17) | ||||
| # of days/week of moderate physical activity 10+ minutes | Primary | 21 | −0.020 | 0.046 | 6.64E-01 | 609 | 0.051 | 2.97E-01 | 0.98(0.90,1.07) | No | - | - |
| Overall activity | Primary | 20 | −0.101 | 0.034 | 3.13E-03 | 620 | −0.038 | 2.89E-01 | 0.90(0.84,0.97) | No | - | - |
| Sedentary behavior | Primary | 20 | 0.052 | 0.036 | 1.46E-01 | 620 | −0.007 | 9.99E-01 | 1.05(0.98,1.13) | No | - | - |
| Sleep duration | Primary | 21 | −0.044 | 0.020 | 2.79E-02 | 609 | −0.039 | 1.00E-01 | 0.96(0.92,1.00) | No | - | - |
| Major depressive disorder | Primary | 18 | 0.227 | 0.070 | 1.22E-03 | 608 | 0.233 | 9.76E-05 | 1.26(1.09,1.44) | Yes | Yes | No |
| Sensitivityd | 1 | −0.124 | 0.145 | 3.91E-01 | 254 | 0.170 | 1.03E-02 | 0.88(0.67,1.17) | ||||
IVW=inverse variance weighted meta-analysis, CAUSE= Causal Analysis Using Summary Effect, SNP=single nucleotide polymorphism, OR = odds ratio
Results highlighted in red are statistically significant (p-value<0.003125 = 0.05/(8*2)); further details of Mendelian randomization results are provided in Supplemental Tables S3, S6, S7
Criterion 1: significant (p <0.003125) associations in IVW or CAUSE
Criterion 2: magnitude and direction of the effect estimates is concordant between IVW and CAUSE
Criterion 3: direction of the effect estimates is concordant between primary analysis and both sensitivity analyses
For CAUSE sensitivity analyses, SNPs associated with other risk factors with p < 5E-7 (22 risk factors, see Table S1) were excluded. For IVW sensitivity analyses, SNPs associated with other risk factors with p < 5E-7 (22 risk factors, see Table S1) were excluded, as were SNPs identifed by MR PRESSO as horizontal pleiotropy outliers.
Mendelian randomization estimates both for IVW and CAUSE were transformed using scaling coefficient (see Table S3 and Supplementary methods)
Odds ratio estimates were obtained from Beta IVW, lower and upper estimates of OR are provided in brackets (95% CI). Of note, ORs reflect 95% CI and therefore do not correlate with the Bonferroni-corrected threshold for statistical significance (p <0.003125).