Polygenic Health Index, General Health, and Pleiotropy: Sibling Analysis and Disease Risk Reduction
Abstract 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...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-10-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-22637-8 |
| _version_ | 1811335368993144832 |
|---|---|
| author | Erik Widen Louis Lello Timothy G. Raben Laurent C. A. M. Tellier Stephen D. H. Hsu |
| author_facet | Erik Widen Louis Lello Timothy G. Raben Laurent C. A. M. Tellier Stephen D. H. Hsu |
| author_sort | Erik Widen |
| collection | DOAJ |
| description | Abstract 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 ten 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. |
| first_indexed | 2024-04-13T17:23:06Z |
| format | Article |
| id | doaj.art-5816da80f15549efb8dc47ae9549ba2b |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-13T17:23:06Z |
| publishDate | 2022-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-5816da80f15549efb8dc47ae9549ba2b2022-12-22T02:37:53ZengNature PortfolioScientific Reports2045-23222022-10-0112111310.1038/s41598-022-22637-8Polygenic Health Index, General Health, and Pleiotropy: Sibling Analysis and Disease Risk ReductionErik Widen0Louis Lello1Timothy G. Raben2Laurent C. A. M. Tellier3Stephen D. H. Hsu4Department of Physics and Astronomy, Michigan State UniversityDepartment of Physics and Astronomy, Michigan State UniversityDepartment of Physics and Astronomy, Michigan State UniversityDepartment of Physics and Astronomy, Michigan State UniversityDepartment of Physics and Astronomy, Michigan State UniversityAbstract 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 ten 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://doi.org/10.1038/s41598-022-22637-8 |
| spellingShingle | Erik Widen Louis Lello Timothy G. Raben Laurent C. A. M. Tellier Stephen D. H. Hsu Polygenic Health Index, General Health, and Pleiotropy: Sibling Analysis and Disease Risk Reduction Scientific Reports |
| title | Polygenic Health Index, General Health, and Pleiotropy: Sibling Analysis and Disease Risk Reduction |
| title_full | Polygenic Health Index, General Health, and Pleiotropy: Sibling Analysis and Disease Risk Reduction |
| title_fullStr | Polygenic Health Index, General Health, and Pleiotropy: Sibling Analysis and Disease Risk Reduction |
| title_full_unstemmed | Polygenic Health Index, General Health, and Pleiotropy: Sibling Analysis and Disease Risk Reduction |
| title_short | Polygenic Health Index, General Health, and Pleiotropy: Sibling Analysis and Disease Risk Reduction |
| title_sort | polygenic health index general health and pleiotropy sibling analysis and disease risk reduction |
| url | https://doi.org/10.1038/s41598-022-22637-8 |
| work_keys_str_mv | AT erikwiden polygenichealthindexgeneralhealthandpleiotropysiblinganalysisanddiseaseriskreduction AT louislello polygenichealthindexgeneralhealthandpleiotropysiblinganalysisanddiseaseriskreduction AT timothygraben polygenichealthindexgeneralhealthandpleiotropysiblinganalysisanddiseaseriskreduction AT laurentcamtellier polygenichealthindexgeneralhealthandpleiotropysiblinganalysisanddiseaseriskreduction AT stephendhhsu polygenichealthindexgeneralhealthandpleiotropysiblinganalysisanddiseaseriskreduction |