Table 2.
Multivariable inverse-variance weighted mendelian randomization association between educational attainment and risk of suicide attempt in individuals with and without mental disorders, adjusted for tobacco smoking behavior, alcohol consumption behaviors, and whether ever seen a general practitioner or psychiatrist for nerves, tension, anxiety or depression.
| Outcome | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Suicide attempt: model 1 | Suicide attempt: model 2 | |||||||||
| Exposures | N SNPS | OR | OR LCI | OR UCI | P-value | N SNPS | OR | OR LCI | OR UCI | P-value |
| SVMR | ||||||||||
| Educational attainment | 223 | 0.524 | 0.412 | 0.666 | 1.07E−07 | 224 | 0.687 | 0.540 | 0.874 | 2.20E−03 |
| Alcohol consumption | 32 | 1.041 | 0.591 | 1.837 | 8.90E−01 | 33 | 1.113 | 0.602 | 2.058 | 7.32E−01 |
| Ever smoker | 54 | 7.017 | 2.660 | 18.602 | 8.26E−05 | 54 | 3.899 | 1.561 | 9.734 | 3.56E−03 |
| Ever seen a GP | 28 | 12.315 | 3.462 | 44.099 | 1.05E−04 | NA | ||||
| Ever seen a psychiatrist | 47 | 28.979 | 5.158 | 164.237 | 1.32E−04 | NA | ||||
| MVMR: Adjusting for alcohol consumption and ever smoker status | ||||||||||
| Educational attainment | 262 | 0.481 | 0.385 | 0.600 | 5.02E−10 | 265 | 0.624 | 0.495 | 0.787 | 8.01E−05 |
| Alcohol consumption | 262 | 0.757 | 0.404 | 1.418 | 3.85E−01 | 265 | 0.781 | 0.407 | 1.497 | 4.57E−01 |
| MVMR: adjusting ever smoker status | ||||||||||
| Educational attainment | 278 | 0.511 | 0.406 | 0.643 | 2.46E−08 | 279 | 0.633 | 0.503 | 0.796 | 1.17E−04 |
| Ever smoker | 278 | 5.778 | 2.143 | 15.576 | 1.00E−03 | 279 | 4.225 | 1.576 | 11.323 | 4.00E−03 |
| MVMR: Adjusting for alcohol consumption and ever smoker status | ||||||||||
| Educational attainment | 263 | 0.500 | 0.389 | 0.642 | 1.42E−07 | 276 | 0.640 | 0.502 | 0.816 | 4.02E−04 |
| Alcohol consumption | 263 | 0.766 | 0.384 | 1.526 | 0.448 | 276 | 0.654 | 0.334 | 1.282 | 2.17E−01 |
| Ever smoker | 263 | 4.141 | 1.412 | 12.146 | 0.01 | 276 | 3.770 | 1.339 | 10.611 | 1.20E−02 |
| MVMR: adjusting for alcohol consumption, ever smoker status, and ever seen GP | ||||||||||
| Educational attainment | 279 | 0.545 | 0.425 | 0.699 | 3.33E−06 | NA | ||||
| Alcohol consumption | 279 | 0.757 | 0.386 | 1.482 | 4.16E−01 | NA | ||||
| Ever smoker | 279 | 4.389 | 1.433 | 13.439 | 1.00E−02 | NA | ||||
| Ever seen a GP | 279 | 2.971 | 0.687 | 12.847 | 1.45E−01 | NA | ||||
| MVMR: adjusting for alcohol consumption, ever smoker status, and ever seen psychiatrist | ||||||||||
| Educational attainment | 279 | 0.541 | 0.421 | 0.696 | 2.84E−06 | NA | ||||
| Alcohol consumption | 279 | 0.768 | 0.390 | 1.513 | 4.46E−01 | NA | ||||
| Ever smoker | 279 | 5.155 | 1.707 | 15.571 | 4.00E−03 | NA | ||||
| Ever seen a psychiatrist | 279 | 8.882 | 0.518 | 152.323 | 1.32E−01 | NA | ||||
Results are presented as odds ratios (OR) with 95% confidence intervals for the effect of a unit standard deviation increase in educational attainment (years of schooling: mean = 16.8, s.d.=4.2 years), a unit increase in alcohol units consumed weekly (mean 15.1, s.d. = 16.6), a unit increase in the log odds of ever smoking (tobacco), a unit increase in the log odds of every having seen a general practitioner (GP) or psychiatrist, respectively, for nerves, tension, anxiety, or depression on the risk of suicide attempt (hospital recorded non-fatal suicide attempt, including secondary diagnoses of poisoning by drugs or other substances, or injuries to hand, wrist, and forearm). Model 1 was based upon iPSYCH Suicide Attempt Risk GWAS not accounting for diagnosed comorbid mental disorders (N = 50,260); model 2 was based upon iPSYCH Suicide Attempt Risk GWAS accounting for diagnosed comorbid mental disorders in same cohort sample (N = 50,260): schizophrenia, bipolar disorder, affective disorders, autism spectrum disorder, anorexia, and “any other disorder”. (1) SVMR results show effects of additional exposures on outcomes analyzed separately: the estimates are considered to be the total effect (direct plus indirect effect) of the exposure on the outcome; (2) MVMR results adjusting for additional exposures show effects of EA analyzed simultaneously with additional exposure (and combinations of exposures): the estimates are interpreted as the direct effect of the exposure on the outcome, independent of the effect of the other exposure. All results shown are pruned of variants identified as outliers by the MR-PRESSO test (MR-PRESSO P < 0.10). Cochran Q tests did not indicate heterogeneity (except as otherwise noted in the text) and MR Egger intercept test did not indicate pleiotropy for any model. See Supplementary Tables 10–12 for full results.
SVMR single-variable Mendelian randomization, MVMR multivariable Mendelian randomization, N number, SNPs single-nucleotide polymorphisms, OR odds ratio, OR LCI 95% confidence interval lower bound, OR UCI 95% confidence interval upper bound.