Polygenic risk scores for prediction of breast cancer risk in Asian populations
<strong>Purpose</strong> Non-European populations are under-represented in genetics studies, hindering clinical implementation of breast cancer polygenic risk scores (PRSs). We aimed to develop PRSs using the largest available studies of Asian ancestry and to assess the transferability o...
| Main Authors: | , , , , , , |
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| Outros autores: | |
| Formato: | Journal article |
| Idioma: | English |
| Publicado: |
American College of Medical Genetics and Genomics
2021
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| _version_ | 1826308232844410880 |
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| author | Ho, W-K Tai, M-C Dennis, J Millwood, IY Lin, K Walters, RG Et al. |
| author2 | BioBank Japan Project |
| author_facet | BioBank Japan Project Ho, W-K Tai, M-C Dennis, J Millwood, IY Lin, K Walters, RG Et al. |
| author_sort | Ho, W-K |
| collection | OXFORD |
| description | <strong>Purpose</strong>
Non-European populations are under-represented in genetics studies, hindering clinical implementation of breast cancer polygenic risk scores (PRSs). We aimed to develop PRSs using the largest available studies of Asian ancestry and to assess the transferability of PRS across ethnic subgroups.
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<strong>Methods</strong>
The development data set comprised 138,309 women from 17 case-control studies. PRSs were generated using a clumping and thresholding method, lasso penalized regression, an Empirical Bayes approach, a Bayesian polygenic prediction approach, or linear combinations of multiple PRSs. These PRSs were evaluated in 89,898 women from 3 prospective studies (1592 incident cases).
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<strong>Results</strong>
The best performing PRS (genome-wide set of single-nucleotide variations [formerly single-nucleotide polymorphism]) had a hazard ratio per unit SD of 1.62 (95% CI = 1.46-1.80) and an area under the receiver operating curve of 0.635 (95% CI = 0.622-0.649). Combined Asian and European PRSs (333 single-nucleotide variations) had a hazard ratio per SD of 1.53 (95% CI = 1.37-1.71) and an area under the receiver operating curve of 0.621 (95% CI = 0.608-0.635). The distribution of the latter PRS was different across ethnic subgroups, confirming the importance of population-specific calibration for valid estimation of breast cancer risk.
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<strong>Conclusion</strong>
PRSs developed in this study, from association data from multiple ancestries, can enhance risk stratification for women of Asian ancestry. |
| first_indexed | 2024-03-07T07:14:57Z |
| format | Journal article |
| id | oxford-uuid:3281b145-1d5b-4dcc-ab22-de6fe60a9306 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:14:57Z |
| publishDate | 2021 |
| publisher | American College of Medical Genetics and Genomics |
| record_format | dspace |
| spelling | oxford-uuid:3281b145-1d5b-4dcc-ab22-de6fe60a93062022-08-09T10:21:50ZPolygenic risk scores for prediction of breast cancer risk in Asian populationsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:3281b145-1d5b-4dcc-ab22-de6fe60a9306EnglishSymplectic ElementsAmerican College of Medical Genetics and Genomics2021Ho, W-KTai, M-CDennis, JMillwood, IYLin, KWalters, RGEt al.BioBank Japan Project<strong>Purpose</strong> Non-European populations are under-represented in genetics studies, hindering clinical implementation of breast cancer polygenic risk scores (PRSs). We aimed to develop PRSs using the largest available studies of Asian ancestry and to assess the transferability of PRS across ethnic subgroups. <br> <strong>Methods</strong> The development data set comprised 138,309 women from 17 case-control studies. PRSs were generated using a clumping and thresholding method, lasso penalized regression, an Empirical Bayes approach, a Bayesian polygenic prediction approach, or linear combinations of multiple PRSs. These PRSs were evaluated in 89,898 women from 3 prospective studies (1592 incident cases). <br> <strong>Results</strong> The best performing PRS (genome-wide set of single-nucleotide variations [formerly single-nucleotide polymorphism]) had a hazard ratio per unit SD of 1.62 (95% CI = 1.46-1.80) and an area under the receiver operating curve of 0.635 (95% CI = 0.622-0.649). Combined Asian and European PRSs (333 single-nucleotide variations) had a hazard ratio per SD of 1.53 (95% CI = 1.37-1.71) and an area under the receiver operating curve of 0.621 (95% CI = 0.608-0.635). The distribution of the latter PRS was different across ethnic subgroups, confirming the importance of population-specific calibration for valid estimation of breast cancer risk. <br> <strong>Conclusion</strong> PRSs developed in this study, from association data from multiple ancestries, can enhance risk stratification for women of Asian ancestry. |
| spellingShingle | Ho, W-K Tai, M-C Dennis, J Millwood, IY Lin, K Walters, RG Et al. Polygenic risk scores for prediction of breast cancer risk in Asian populations |
| title | Polygenic risk scores for prediction of breast cancer risk in Asian populations |
| title_full | Polygenic risk scores for prediction of breast cancer risk in Asian populations |
| title_fullStr | Polygenic risk scores for prediction of breast cancer risk in Asian populations |
| title_full_unstemmed | Polygenic risk scores for prediction of breast cancer risk in Asian populations |
| title_short | Polygenic risk scores for prediction of breast cancer risk in Asian populations |
| title_sort | polygenic risk scores for prediction of breast cancer risk in asian populations |
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