Background
Methods
Population
Exposures and outcomes
Physical activity (PA) and sedentary time (ST)
Depression, anxiety and well-being
Depression
Anxiety
Well-being
Analysing associations between exposures and outcomes
Observational association analysis in the UK Biobank
Mendelian randomisation analysis
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The exposure SNPs are robustly associated with the relevant measured exposure. This is quantified by the F-statistic, which can be approximated by the ratio of the SNP-exposure association estimate, \(\widehat{\beta }\) and its standard error, \(SE(\widehat{\beta })\), squared (Eq. 1) [33].$$\mathrm{F }= {\left(\frac{\widehat{\beta }}{{SE(\widehat{\beta })}}\right)}^{2}$$(1)
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The exposure SNPs are not associated with confounding factors that bias conventional epidemiological associations.
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The exposure SNPs are only associated with the outcome through the risk factor.
Bidirectional analyses
Sex stratified analysis
Sensitivity analysis
Results
Trait | All | Females | Males |
---|---|---|---|
N | 145,982 | 82,437 | 63,545 |
Age (years) | 56.56 (7.70) | 56.08 (7.63) | 57.19 (7.75) |
Body mass index (kg/m2) | 26.78 (4.55) | 26.35 (4.88) | 27.33 (4.01) |
Townsend deprivation index | − 1.79 (2.78) | − 1.75 (2.77) | − 1.83 (2.80) |
Sedentary time (hours/day) | 9.18 (2.35) | 8.89 (2.24) | 9.55 (2.43) |
Major depression — N cases (%) | 34,858 (23.88) | 24,022 (29.14) | 10,836 (17.05) |
Current depression — N cases (%) | 2659 (1.82) | 1691 (2.05) | 968 (1.52) |
Generalised anxiety disorder — N cases (%) | 7244 (4.96) | 4706 (5.71) | 2536 (3.99) |
Current generalised anxiety disorder — N cases (%) | 1854 (1.27) | 1205 (1.46) | 649 (1.02) |
Severity of major depression | 3 [6] | 4 [6] | 0 [5] |
Severity of current depression | 2 [4] | 2 [4] | 1 [3] |
Severity of generalised anxiety disorder | 0 [3] | 1 [4] | 0 [2] |
Well-being score | 13 [3] | 13 [3] | 13 [3] |
Observational associations in UK Biobank MHQ
Our MR analyses used valid instruments
Genetically instrumented higher PA was associated with lower odds and severity of depression whilst ST was not associated with depression
Exposure | Outcome | Strata | OR (95% CI) | P |
Physical activity | PGC-Depression | All | 0.93 (0.88; 0.97) | 1.58E − 03 |
Physical activity | PGC-Anxiety | All | 1.11 (0.84; 1.47) | 4.75E − 01 |
Exposure | Outcome | Strata | OR (95% CI) | P |
Physical activity | Current depression | All | 0.99 (0.93; 1.04) | 5.91E − 01 |
Females | 0.99 (0.92; 1.07) | 8.37E − 01 | ||
Males | 0.97 (0.89; 1.06) | 4.81E − 01 | ||
Physical activity | Lifetime major depression | All | 1.00 (0.93; 1.08) | 9.44E − 01 |
Females | 1.01 (0.93; 1.10) | 7.69E − 01 | ||
Males | 0.99 (0.89; 1.09) | 8.24E − 01 | ||
Physical activity | Current anxiety disorder | All | 0.95 (0.88; 1.03) | 1.93E − 01 |
Females | 0.96 (0.87; 1.06) | 4.07E − 01 | ||
Males | 0.94 (0.84; 1.04) | 2.18E − 01 | ||
Physical activity | Lifetime anxiety disorder | All | 0.99 (0.92; 1.06) | 7.99E − 01 |
Females | 0.98 (0.89; 1.08) | 6.78E − 01 | ||
Males | 0.99 (0.89; 1.09) | 7.64E − 01 | ||
Exposure | Outcome | Strata | Beta (SE) | P |
Physical activity | Well-being | All | 0.11 (0.04; 0.18) | 1.41E − 03 |
Females | 0.12 (0.03; 0.21) | 8.32E − 03 | ||
Males | 0.09 (0.01; 0.18) | 3.40E − 02 | ||
Physical activity | Severity of major depression | All | − 0.01 (− 0.09; 0.08) | 8.68E − 01 |
Females | − 0.03 (− 0.12; 0.07) | 5.92E − 01 | ||
Males | 0.02 (− 0.09; 0.13) | 7.18E − 01 | ||
Physical activity | Severity of current depression | All | − 0.11 (− 0.18; − 0.04) | 1.60E − 03 |
Females | − 0.14 (− 0.22; − 0.05) | 2.18E − 03 | ||
Males | − 0.08 (− 0.17; 0.01) | 7.67E − 02 | ||
Physical activity | Severity of anxiety | All | − 0.03 (− 0.10; 0.04) | 3.65E − 01 |
Females | − 0.08 (− 0.17; 0.01) | 7.09E − 02 | ||
Males | 0.04 (− 0.06; 0.13) | 4.29E − 01 | ||
Physical activity | Subjective well-being (GWAS) | All | − 0.03 (− 0.18; 0.11) | 6.74E − 01 |
Exposure | Outcome | Strata | OR (95% CI) | P |
Sedentary time | PGC-Depression | All | 0.96 (0.86; 1.07) | 4.38E − 01 |
Sedentary time | PGC-Anxiety | All | 2.25 (1.10; 4.60) | 2.59E − 02 |
Exposure | Outcome | Strata | Odds ratio (95% CI) | P |
Sedentary time | Current depression | All | 0.95 (0.84; 1.07) | 4.01E − 01 |
Females | 0.96 (0.82; 1.12) | 5.97E − 01 | ||
Males | 0.94 (0.76; 1.16) | 5.80E − 01 | ||
Sedentary time | Lifetime major depression | All | 1.06 (0.93; 1.20) | 3.97E − 01 |
Females | 1.08 (0.92; 1.26) | 3.62E − 01 | ||
Males | 1.02 (0.85; 1.22) | 8.41E − 01 | ||
Sedentary time | Current anxiety disorder | All | 0.98 (0.83; 1.15) | 7.55E − 01 |
Females | 0.88 (0.71; 1.08) | 2.15E − 01 | ||
Males | 1.13 (0.88; 1.44) | 3.43E − 01 | ||
Sedentary time | Lifetime anxiety disorder | All | 0.97 (0.83; 1.12) | 6.34E − 01 |
Females | 0.95 (0.78; 1.17) | 6.47E − 01 | ||
Males | 0.99 (0.79; 1.25) | 9.50E − 01 | ||
Exposure | Outcome | Strata | Beta (SE) | P |
Sedentary time | Well-being | All | − 0.18 (− 0.33; − 0.04) | 1.46E − 02 |
Females | − 0.14 (− 0.31; 0.03) | 1.14E − 01 | ||
Males | − 0.23 (− 0.44; − 0.02) | 2.91E − 02 | ||
Sedentary time | Severity of major depression | All | 0.08 (− 0.06; 0.22) | 2.47E − 01 |
Females | 0.04 (− 0.12; 0.20) | 6.26E − 01 | ||
Males | 0.14 (− 0.09; 0.37) | 2.43E − 01 | ||
Sedentary time | Severity of current depression | All | 0.05 (− 0.08; 0.18) | 4.69E − 01 |
Females | 0.06 (− 0.11; 0.23) | 4.73E − 01 | ||
Males | 0.03 (− 0.16; 0.22) | 7.60E − 01 | ||
Sedentary time | Severity of anxiety | All | 0.004 (− 0.12; 0.13) | 9.52E − 01 |
Females | 0.04 (− 0.12; 0.20) | 6.12E − 01 | ||
Males | − 0.02 (− 0.22; 0.17) | 8.12E − 01 | ||
Sedentary time | Subjective well-being (GWAS) | All | 0.10 (− 0.35; 0.56) | 6.59E − 01 |
Genetically instrumented higher PA was not associated with anxiety, whilst ST associated with lower odds of anxiety
Genetically instrumented higher PA and ST was associated with well-being in opposite directions
Bidirectional results
Exposure | Outcome | Strata | Beta (95% CI) | P |
Depression | Overall physical activity | All | − 0.25 (− 0.42; − 0.08) | 4.07E − 03 |
Females | − 0.45 (− 0.67; − 0.23) | 6.05E − 05 | ||
Males | − 0.08 (− 0.27; 0.11) | 4.21E − 01 | ||
Depression | Sedentary time | All | 0.04 (− 0.11; 0.18) | 6.33E − 01 |
Females | 0.17 (− 0.03; 0.36) | 9.32E − 02 | ||
Males | − 0.08 (− 0.28; 0.12) | 4.13E − 01 | ||
Exposure | Outcome | Strata | Beta (95% CI) | P |
Anxiety | Overall physical activity | All | 0.00 (− 0.08; 0.08) | 9.48E − 01 |
Females | 0.01 (− 0.10; 0.10) | 8.24E − 01 | ||
Males | − 0.01 (-0.11; 0.10) | 8.99E − 01 | ||
Anxiety | Sedentary time | All | − 0.02 (− 0.13; 0.08) | 9.99E − 01 |
Females | − 0.04 (− 0.18; 0.09) | 5.34E − 01 | ||
Males | 0.00 (− 0.13; 0.12) | 9.46E − 01 | ||
Exposure | Outcome | Strata | Beta (95% CI) | P |
Well-being GWAS | Overall physical activity | All | 0.13 (− 0.06; 0.31) | 1.68E − 01 |
Females | 0.07 (− 0.17; 0.31) | 5.71E − 01 | ||
Males | 0.16 (− 0.04; 0.36) | 1.21E − 01 | ||
Well-being GWAS | Sedentary time | All | 0.07 (− 0.09; 0.23) | 3.87E − 01 |
Females | 0.05 (− 0.18; 0.28) | 6.54E − 01 | ||
Males | 0.10 (− 0.10; 0.29) | 3.27E − 01 | ||
Well-being from UKB | Overall physical activity | All | 0.15 (0.05; 0.25) | 4.65E − 03 |
Females | 0.18 (0.04; 0.33) | 1.33E − 02 | ||
Males | 0.12 (− 0.002; 0.24) | 5.40E − 02 | ||
Well-being from UKB | Sedentary time | All | − 0.02 (− 0.12; 0.09) | 7.14E − 01 |
Females | − 0.05 (− 0.19; 0.09) | 4.75E − 01 | ||
Males | 0.00 (− 0.12; 0.12) | 9.87E − 01 |
Sex-stratified analyses
Sensitivity analyses
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1. Excluding known loci
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2. IVW, Egger and weighted median
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3. Different p-value thresholds
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4. 2-sample MR with non-overlapping depression GWAS
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5. Individual well-being questions from MHQ