Heterogeneous associations of polygenic indices of 35 traits with mortality: a register-linked population-based follow-up study
- Helsinki Institute for Demography and Population Health, University of Helsinki, Finland
- Max Planck – University of Helsinki Center for Social Inequalities in Population Health, Finland
- Institute for Molecular Medicine FIMM, University of Helsinki, Finland
- FIMM, University of Helsinki, Finland
- VATT Institute for Economic Research, Finland
- Institute of Labor Economics (IZA), Germany
Figures
Figure 1
Hazard ratios of polygenic indices for all-cause mortality.
Population (N=40,097 individuals) and within-sibship (N=10,174 individuals in 5071 sibships) estimates. Estimates from Cox proportional hazards models adjusted for indicators for the baseline year, sex and 10 first principal components of the genome. Capped bars are 95% confidence intervals. For a table of corresponding estimates, see Supplementary file 1E. Abbreviations: HR = Hazard ratio; ADHD = Attention deficit hyperactivity disorder.
Figure 2
Hazard ratios of polygenic indices for all-cause mortality by sex (Panel A), educational group (Panel B), age-specific mortality follow-up period (Panel C), and cause of death (Panel D).
Estimates from Cox proportional hazards models adjusted for indicators for the baseline year, sex and 10 first principal components of the genome. Capped bars are 95% confidence intervals. N=40,097 individuals. For a table of corresponding estimates, see Supplementary file 1F. Abbreviations: HR = Hazard ratio; ADHD = Attention deficit hyperactivity disorder.
Tables
Table 1
Hazard ratios of selected polygenic indices and corresponding phenotypes for all-cause mortality (N: 37,548 individuals; 5407 deaths).
All presented variables were standardised to standard-deviation units. For corresponding models with categorical phenotypes, see Supplementary file 1G.
| Model 1 a–1 l | Model 2 a–2 f | Model 3 a & 3b | Model 4 | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| HR | 95% CI | HR | 95% CI | HR | 95% CI | HR | 95% CI | |||||
| lower | upper | lower | upper | lower | upper | lower | upper | |||||
| Smoking | 1.41 | 1.37 | 1.45 | 1.39 | 1.35 | 1.44 | 1.35 | 1.31 | 1.40 | 1.34 | 1.29 | 1.38 |
| PGI-ever smoking | 1.12 | 1.09 | 1.15 | 1.07 | 1.04 | 1.10 | 1.07 | 1.04 | 1.10 | 1.04 | 1.01 | 1.08 |
| BMI | 1.07 | 1.04 | 1.10 | 1.05 | 1.01 | 1.08 | 1.02 | 0.99 | 1.05 | 1.00 | 0.97 | 1.04 |
| PGI-BMI | 1.10 | 1.07 | 1.13 | 1.08 | 1.05 | 1.11 | 1.05 | 1.02 | 1.09 | 1.03 | 1.00 | 1.06 |
| Depression indicators | 1.16 | 1.14 | 1.19 | 1.16 | 1.13 | 1.19 | 1.06 | 1.03 | 1.08 | 1.05 | 1.03 | 1.08 |
| PGI-depressive symptoms | 1.07 | 1.04 | 1.10 | 1.06 | 1.03 | 1.09 | 1.02 | 0.99 | 1.05 | 1.00 | 0.97 | 1.03 |
| Alcohol intake | 1.16 | 1.13 | 1.19 | 1.15 | 1.12 | 1.18 | 1.12 | 1.09 | 1.14 | 1.11 | 1.08 | 1.14 |
| PGI drinks per week | 1.06 | 1.03 | 1.09 | 1.05 | 1.02 | 1.08 | 1.05 | 1.02 | 1.08 | 1.03 | 1.00 | 1.06 |
| Education years | 0.86 | 0.83 | 0.88 | 0.87 | 0.84 | 0.90 | 0.90 | 0.88 | 0.93 | 0.91 | 0.88 | 0.94 |
| PGI educational attainment | 0.91 | 0.89 | 0.94 | 0.94 | 0.92 | 0.97 | 0.96 | 0.93 | 0.99 | 1.02 | 0.99 | 1.05 |
| Self-rated health | 0.74 | 0.72 | 0.76 | 0.75 | 0.73 | 0.77 | 0.77 | 0.75 | 0.80 | 0.78 | 0.75 | 0.80 |
| PGI self-rated health | 0.90 | 0.88 | 0.93 | 0.94 | 0.91 | 0.96 | 0.95 | 0.92 | 0.99 | 0.98 | 0.94 | 1.01 |
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All models adjusted for baseline covariates: indicators of the baseline year, sex, and ten first principal components of the genome.
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Models 1: Baseline covariates + each phenotype/PGI separately.
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Models 2: PGI and corresponding phenotype mutually adjusted.
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Model 3 a: Phenotypes mutually adjusted, Model 3b: PGIs mutually adjusted.
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Model 4: Full model.
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HR=Hazard ratio.
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95% CI=95% confidence interval.
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PGI=Polygenic index.
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BMI=Body mass index.
Table 2
Hazard ratios of selected polygenic indices for all-cause mortality regarding belonging to a risk category in the related phenotypes.
‘Without phenotype’ categories consist of: Never smokers (N: 21,189), BMI 18.5–24.9 (N:15,092), no depression indicators (N: 31,089), non-alcohol drinkers (N: 5498), higher-tertiary-degree holders (N: 4765), the best self-rated health (5-point scale, N: 7566). ‘With phenotype’ categories are those in the population sample with valid information on the phenotype in question excluding the ‘without risk factor’ category.
| Without phenotype | With phenotype | |||||
|---|---|---|---|---|---|---|
| HR | 95% CI | HR | 95% CI | |||
| lower | upper | lower | upper | |||
| PGI-ever smoking | 1.07 | 1.03 | 1.11 | 1.09 | 1.05 | 1.12 |
| PGI-BMI | 1.13 | 1.08 | 1.19 | 1.09 | 1.06 | 1.13 |
| PGI-depressive symptoms | 1.05 | 1.02 | 1.08 | 1.06 | 1.01 | 1.12 |
| PGI-drinks per week | 1.09 | 1.04 | 1.15 | 1.07 | 1.03 | 1.10 |
| PGI-educational attainment | 0.88 | 0.76 | 1.02 | 0.93 | 0.90 | 0.96 |
| PGI-self-rated health | 0.88 | 0.80 | 0.96 | 0.91 | 0.89 | 0.94 |
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All models adjusted for indicators of the baseline year, sex, and ten first principal components of the genome.
-
HR=Hazard ratio.
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95% CI=95% confidence interval.
-
PGI=Polygenic index.
-
BMI=Body mass index.
Additional files
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Supplementary file 1
Supplementary Tables.
- https://cdn.elifesciences.org/articles/107496/elife-107496-supp1-v1.xlsx
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MDAR checklist
- https://cdn.elifesciences.org/articles/107496/elife-107496-mdarchecklist1-v1.pdf
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Heterogeneous associations of polygenic indices of 35 traits with mortality: a register-linked population-based follow-up study
eLife 14:RP107496.
https://doi.org/10.7554/eLife.107496.3
