Informal summary: We built a polygenic health index using risk predictors weighted by lifespan impact of the specific disease condition. This index seems to characterize general health. Individuals with higher index scores have decreased disease risk across almost all 20 diseases (no significant risk increases), and longer calculated life expectancy. When estimated Disability Adjusted Life Years (DALYs) are used as the performance metric, the gain from selection among 10 individuals (highest index score vs average) is found to be roughly 4 DALYs. We find no statistical evidence for antagonistic trade-offs in risk reduction across these diseases. Correlations between genetic disease risks are found to be mostly positive and generally mild.
Some figures:
Polygenic Health Index, General Health, and Disease Risk
We construct a polygenic health index as a weighted sum of polygenic risk scores for 20 major disease conditions, including, e.g., coronary artery disease, type 1 and 2 diabetes, schizophrenia, etc. Individual weights are determined by population-level estimates of impact on life expectancy. We validate this index in odds ratios and selection experiments using unrelated individuals and siblings (pairs and trios) from the UK Biobank. Individuals with higher index scores have decreased disease risk across almost all 20 diseases (no significant risk increases), and longer calculated life expectancy. When estimated Disability Adjusted Life Years (DALYs) are used as the performance metric, the gain from selection among 10 individuals (highest index score vs average) is found to be roughly 4 DALYs. We find no statistical evidence for antagonistic trade-offs in risk reduction across these diseases. Correlations between genetic disease risks are found to be mostly positive and generally mild. These results have important implications for public health and also for fundamental issues such as pleiotropy and genetic architecture of human disease conditions.
https://www.medrxiv.org/content/10.1101/2022.06.15.22276102v1
Extrapolating the DALY gain vs Health Index score curve (top figure) to the entire human population (e.g., 10 billion people) results in +30 or +40 DALYs more than average, or something like 120 total years of life. The individual with the highest Health Index score in the world is predicted to live about 120 years.
I wanted to use this in the paper but my collaborators vetoed me 8-)
The days of our years are threescore years and ten; and if by reason of strength they be fourscore years, yet is their strength labour and sorrow; for it is soon cut off, and we fly away
Psalm 90:10
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