Performance of polygenic risk scores in screening, prediction, and risk stratification: secondary analysis of data in the Polygenic Score Catalog
Objective To clarify the performance of polygenic risk scores in population screening, individual risk prediction, and population risk stratification.Design Secondary analysis of data in the Polygenic Score Catalog.Setting Polygenic Score Catalog, April 2022. Secondary analysis of 3915 performance m...
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BMJ Publishing Group
2023-07-01
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| Series: | BMJ Medicine |
| Online Access: | https://bmjmedicine.bmj.com/content/2/1/e000554.full |
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| author | Harry Hemingway Riyaz Patel Joan K Morris Aroon D Hingorani Reecha Sofat Claudia Langenberg Nicholas J Wald Valerie Kuan Chris Finan Jasmine Gratton A Floriaan Schmidt |
| author_facet | Harry Hemingway Riyaz Patel Joan K Morris Aroon D Hingorani Reecha Sofat Claudia Langenberg Nicholas J Wald Valerie Kuan Chris Finan Jasmine Gratton A Floriaan Schmidt |
| author_sort | Harry Hemingway |
| collection | DOAJ |
| description | Objective To clarify the performance of polygenic risk scores in population screening, individual risk prediction, and population risk stratification.Design Secondary analysis of data in the Polygenic Score Catalog.Setting Polygenic Score Catalog, April 2022. Secondary analysis of 3915 performance metric estimates for 926 polygenic risk scores for 310 diseases to generate estimates of performance in population screening, individual risk, and population risk stratification.Participants Individuals contributing to the published studies in the Polygenic Score Catalog.Main outcome measures Detection rate for a 5% false positive rate (DR5) and the population odds of becoming affected given a positive result; individual odds of becoming affected for a person with a particular polygenic score; and odds of becoming affected for groups of individuals in different portions of a polygenic risk score distribution. Coronary artery disease and breast cancer were used as illustrative examples.Results For performance in population screening, median DR5 for all polygenic risk scores and all diseases studied was 11% (interquartile range 8-18%). Median DR5 was 12% (9-19%) for polygenic risk scores for coronary artery disease and 10% (9-12%) for breast cancer. The population odds of becoming affected given a positive results were 1:8 for coronary artery disease and 1:21 for breast cancer, with background 10 year odds of 1:19 and 1:41, respectively, which are typical for these diseases at age 50. For individual risk prediction, the corresponding 10 year odds of becoming affected for individuals aged 50 with a polygenic risk score at the 2.5th, 25th, 75th, and 97.5th centiles were 1:54, 1:29, 1:15, and 1:8 for coronary artery disease and 1:91, 1:56, 1:34, and 1:21 for breast cancer. In terms of population risk stratification, at age 50, the risk of coronary artery disease was divided into five groups, with 10 year odds of 1:41 and 1:11 for the lowest and highest quintile groups, respectively. The 10 year odds was 1:7 for the upper 2.5% of the polygenic risk score distribution for coronary artery disease, a group that contributed 7% of cases. The corresponding estimates for breast cancer were 1:72 and 1:26 for the lowest and highest quintile groups, and 1:19 for the upper 2.5% of the distribution, which contributed 6% of cases.Conclusion Polygenic risk scores performed poorly in population screening, individual risk prediction, and population risk stratification. Strong claims about the effect of polygenic risk scores on healthcare seem to be disproportionate to their performance. |
| format | Article |
| id | doaj-art-c69e54411b7f40da9fe90317bc2b73ca |
| institution | DOAJ |
| issn | 2754-0413 |
| language | English |
| publishDate | 2023-07-01 |
| publisher | BMJ Publishing Group |
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| spelling | doaj-art-c69e54411b7f40da9fe90317bc2b73ca2025-08-20T03:09:54ZengBMJ Publishing GroupBMJ Medicine2754-04132023-07-012110.1136/bmjmed-2023-000554Performance of polygenic risk scores in screening, prediction, and risk stratification: secondary analysis of data in the Polygenic Score CatalogHarry Hemingway0Riyaz Patel1Joan K Morris2Aroon D Hingorani3Reecha Sofat4Claudia Langenberg5Nicholas J Wald6Valerie Kuan7Chris Finan8Jasmine Gratton9A Floriaan Schmidt10University College London, London, UK1 Department of Cardiology, Barts Heart Centre, Barts Health NHS Trust, London, UKPopulation Health Research Institute, City St George`s University of London, London, UKHealth Data Research UK, London, UKHealth Data Research UK, London, UKPrecision Healthcare University Research Institute, Queen Mary University of London, London, UKInstitute of Health Informatics, University College London, London, UKInstitute of Cardiovascular Science, University College London, London, UKInstitute of Cardiovascular Science, University College London, London, UKInstitute of Cardiovascular Science, University College London, London, UKInstitute of Cardiovascular Science, University College London, London, UKObjective To clarify the performance of polygenic risk scores in population screening, individual risk prediction, and population risk stratification.Design Secondary analysis of data in the Polygenic Score Catalog.Setting Polygenic Score Catalog, April 2022. Secondary analysis of 3915 performance metric estimates for 926 polygenic risk scores for 310 diseases to generate estimates of performance in population screening, individual risk, and population risk stratification.Participants Individuals contributing to the published studies in the Polygenic Score Catalog.Main outcome measures Detection rate for a 5% false positive rate (DR5) and the population odds of becoming affected given a positive result; individual odds of becoming affected for a person with a particular polygenic score; and odds of becoming affected for groups of individuals in different portions of a polygenic risk score distribution. Coronary artery disease and breast cancer were used as illustrative examples.Results For performance in population screening, median DR5 for all polygenic risk scores and all diseases studied was 11% (interquartile range 8-18%). Median DR5 was 12% (9-19%) for polygenic risk scores for coronary artery disease and 10% (9-12%) for breast cancer. The population odds of becoming affected given a positive results were 1:8 for coronary artery disease and 1:21 for breast cancer, with background 10 year odds of 1:19 and 1:41, respectively, which are typical for these diseases at age 50. For individual risk prediction, the corresponding 10 year odds of becoming affected for individuals aged 50 with a polygenic risk score at the 2.5th, 25th, 75th, and 97.5th centiles were 1:54, 1:29, 1:15, and 1:8 for coronary artery disease and 1:91, 1:56, 1:34, and 1:21 for breast cancer. In terms of population risk stratification, at age 50, the risk of coronary artery disease was divided into five groups, with 10 year odds of 1:41 and 1:11 for the lowest and highest quintile groups, respectively. The 10 year odds was 1:7 for the upper 2.5% of the polygenic risk score distribution for coronary artery disease, a group that contributed 7% of cases. The corresponding estimates for breast cancer were 1:72 and 1:26 for the lowest and highest quintile groups, and 1:19 for the upper 2.5% of the distribution, which contributed 6% of cases.Conclusion Polygenic risk scores performed poorly in population screening, individual risk prediction, and population risk stratification. Strong claims about the effect of polygenic risk scores on healthcare seem to be disproportionate to their performance.https://bmjmedicine.bmj.com/content/2/1/e000554.full |
| spellingShingle | Harry Hemingway Riyaz Patel Joan K Morris Aroon D Hingorani Reecha Sofat Claudia Langenberg Nicholas J Wald Valerie Kuan Chris Finan Jasmine Gratton A Floriaan Schmidt Performance of polygenic risk scores in screening, prediction, and risk stratification: secondary analysis of data in the Polygenic Score Catalog BMJ Medicine |
| title | Performance of polygenic risk scores in screening, prediction, and risk stratification: secondary analysis of data in the Polygenic Score Catalog |
| title_full | Performance of polygenic risk scores in screening, prediction, and risk stratification: secondary analysis of data in the Polygenic Score Catalog |
| title_fullStr | Performance of polygenic risk scores in screening, prediction, and risk stratification: secondary analysis of data in the Polygenic Score Catalog |
| title_full_unstemmed | Performance of polygenic risk scores in screening, prediction, and risk stratification: secondary analysis of data in the Polygenic Score Catalog |
| title_short | Performance of polygenic risk scores in screening, prediction, and risk stratification: secondary analysis of data in the Polygenic Score Catalog |
| title_sort | performance of polygenic risk scores in screening prediction and risk stratification secondary analysis of data in the polygenic score catalog |
| url | https://bmjmedicine.bmj.com/content/2/1/e000554.full |
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