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. Author manuscript; available in PMC: 2023 Jul 1.
Published in final edited form as: Eur Spine J. 2022 Jun 4;31(7):1906–1915. doi: 10.1007/s00586-022-07263-2

Table 2.

Mendelian randomization estimates for the causal effect of risk factors on chronic back pain (CBP)

IVW analysis CAUSE analysis
Exposure Analysis type # of SNPs Beta SE p-value # of SNPs Gamma p-value ORf Criterion 1a Criterion 2b Criterion 3c
Years of schooling Primary 304 −0.612 0.040 3.0E-53 972 −0.547 2.2E-08 0.54(0.50,0.59) Yes Yes Yes
Sensitivityd 118 −0.547 0.055 6.7E-23 486 −0.462 2.0E-05 0.58(0.52,0.65)
Ever smokere Primary 133 0.238 0.031 7.0E-15 809 0.227 0.0001 1.27(1.19,1.35) Yes Yes Yes
Sensitivityd 39 0.132 0.047 4.9E-03 350 0.164 0.013 1.14(1.04,1.25)
Alcohol intake frequency Primary 94 0.254 0.051 7.2E-07 773 0.261 0.029 1.29(1.17,1.43) Yes Yes Yes
Sensitivityd 21 0.074 0.067 2.7E-01 312 0.145 0.069 1.08(0.94,1.23)
# of days/week of moderate physical activity 10+ minutes Primary 16 −0.030 0.083 7.2E-01 579 0.007 0.99 0.97(0.82,1.14) No - -
Overall activity Primary 6 −0.130 0.167 4.4E-01 541 −0.104 0.39 0.88(0.63,1.22) No - -
Sedentary behavior Primary 5 −0.149 0.093 1.1E-01 490 0.040 0.88 0.86(0.72,1.03) No - -
Sleep duration Primary 65 −0.322 0.116 5.4E-03 715 −0.373 0.002 0.72(0.58,0.91) Yes Yes No
Sensitivityd 14 0.037 0.157 8.1E-01 310 −0.409 0.026 1.04(0.76,1.41)
Major depressive disorder Primary 46 0.347 0.055 2.5E-10 662 0.291 0.017 1.41(1.27,1.58) Yes Yes Yes
Sensitivityd 6 0.402 0.092 1.3E-05 279 0.263 0.002 1.49(1.25,1.79)

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 S2, S4, S5

a

Criterion 1: significant (p <0.003125) associations in IVW or CAUSE

b

Criterion 2: magnitude and direction of the effect estimates is concordant between IVW and CAUSE

c

Criterion 3: direction of the effect estimates is concordant between primary analysis and both sensitivity analyses

d

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.

e

Mendelian randomization estimates both for IVW and CAUSE were transformed using scaling coefficient (see Table S2 and Supplementary methods)

f

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).