The frequency of pathogenic variation in the All of Us cohort reveals ancestry-driven disparities
Abstract Disparities in data underlying clinical genomic interpretation is an acknowledged problem, but there is a paucity of data demonstrating it. The All of Us Research Program is collecting data including whole-genome sequences, health records, and surveys for at least a million participants wit...
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| Format: | Article |
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Nature Portfolio
2024-02-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-023-05708-y |
| _version_ | 1827222280483110912 |
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| author | Eric Venner Karynne Patterson Divya Kalra Marsha M. Wheeler Yi-Ju Chen Sara E. Kalla Bo Yuan Jason H. Karnes Kimberly Walker Joshua D. Smith Sean McGee Aparna Radhakrishnan Andrew Haddad Philip E. Empey Qiaoyan Wang Lee Lichtenstein Diana Toledo Gail Jarvik Anjene Musick Richard A. Gibbs the All of Us Research Program Investigators |
| author_facet | Eric Venner Karynne Patterson Divya Kalra Marsha M. Wheeler Yi-Ju Chen Sara E. Kalla Bo Yuan Jason H. Karnes Kimberly Walker Joshua D. Smith Sean McGee Aparna Radhakrishnan Andrew Haddad Philip E. Empey Qiaoyan Wang Lee Lichtenstein Diana Toledo Gail Jarvik Anjene Musick Richard A. Gibbs the All of Us Research Program Investigators |
| author_sort | Eric Venner |
| collection | DOAJ |
| description | Abstract Disparities in data underlying clinical genomic interpretation is an acknowledged problem, but there is a paucity of data demonstrating it. The All of Us Research Program is collecting data including whole-genome sequences, health records, and surveys for at least a million participants with diverse ancestry and access to healthcare, representing one of the largest biomedical research repositories of its kind. Here, we examine pathogenic and likely pathogenic variants that were identified in the All of Us cohort. The European ancestry subgroup showed the highest overall rate of pathogenic variation, with 2.26% of participants having a pathogenic variant. Other ancestry groups had lower rates of pathogenic variation, including 1.62% for the African ancestry group and 1.32% in the Latino/Admixed American ancestry group. Pathogenic variants were most frequently observed in genes related to Breast/Ovarian Cancer or Hypercholesterolemia. Variant frequencies in many genes were consistent with the data from the public gnomAD database, with some notable exceptions resolved using gnomAD subsets. Differences in pathogenic variant frequency observed between ancestral groups generally indicate biases of ascertainment of knowledge about those variants, but some deviations may be indicative of differences in disease prevalence. This work will allow targeted precision medicine efforts at revealed disparities. |
| first_indexed | 2024-03-07T14:45:23Z |
| format | Article |
| id | doaj.art-1c6ea528141443f1ab6c586d02aa9e33 |
| institution | Directory Open Access Journal |
| issn | 2399-3642 |
| language | English |
| last_indexed | 2025-03-21T16:35:59Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj.art-1c6ea528141443f1ab6c586d02aa9e332024-06-16T11:30:35ZengNature PortfolioCommunications Biology2399-36422024-02-017111110.1038/s42003-023-05708-yThe frequency of pathogenic variation in the All of Us cohort reveals ancestry-driven disparitiesEric Venner0Karynne Patterson1Divya Kalra2Marsha M. Wheeler3Yi-Ju Chen4Sara E. Kalla5Bo Yuan6Jason H. Karnes7Kimberly Walker8Joshua D. Smith9Sean McGee10Aparna Radhakrishnan11Andrew Haddad12Philip E. Empey13Qiaoyan Wang14Lee Lichtenstein15Diana Toledo16Gail Jarvik17Anjene Musick18Richard A. Gibbs19the All of Us Research Program InvestigatorsHuman Genome Sequencing Center, Baylor College of MedicineDepartment of Genome Sciences, University of WashingtonHuman Genome Sequencing Center, Baylor College of MedicineDepartment of Genome Sciences, University of WashingtonHuman Genome Sequencing Center, Baylor College of MedicineHuman Genome Sequencing Center, Baylor College of MedicineHuman Genome Sequencing Center, Baylor College of MedicineUniversity of Arizona, R Ken Coit College of Pharmacy, Department of Pharmacy Practice and ScienceHuman Genome Sequencing Center, Baylor College of MedicineDepartment of Genome Sciences, University of WashingtonDepartment of Genome Sciences, University of WashingtonDepartment of Genome Sciences, University of WashingtonDepartment of Pharmaceutical Sciences, University of Pittsburgh School of PharmacyDepartment of Pharmacy and Therapeutics, University of Pittsburgh School of PharmacyHuman Genome Sequencing Center, Baylor College of MedicineBroad Institute of MIT and HarvardBroad Institute of MIT and HarvardDepartment of Medicine (Medical Genetics), University of Washington School of MedicineNIH All of Us Research Program, National Institutes of Health Office of the DirectorHuman Genome Sequencing Center, Baylor College of MedicineAbstract Disparities in data underlying clinical genomic interpretation is an acknowledged problem, but there is a paucity of data demonstrating it. The All of Us Research Program is collecting data including whole-genome sequences, health records, and surveys for at least a million participants with diverse ancestry and access to healthcare, representing one of the largest biomedical research repositories of its kind. Here, we examine pathogenic and likely pathogenic variants that were identified in the All of Us cohort. The European ancestry subgroup showed the highest overall rate of pathogenic variation, with 2.26% of participants having a pathogenic variant. Other ancestry groups had lower rates of pathogenic variation, including 1.62% for the African ancestry group and 1.32% in the Latino/Admixed American ancestry group. Pathogenic variants were most frequently observed in genes related to Breast/Ovarian Cancer or Hypercholesterolemia. Variant frequencies in many genes were consistent with the data from the public gnomAD database, with some notable exceptions resolved using gnomAD subsets. Differences in pathogenic variant frequency observed between ancestral groups generally indicate biases of ascertainment of knowledge about those variants, but some deviations may be indicative of differences in disease prevalence. This work will allow targeted precision medicine efforts at revealed disparities.https://doi.org/10.1038/s42003-023-05708-y |
| spellingShingle | Eric Venner Karynne Patterson Divya Kalra Marsha M. Wheeler Yi-Ju Chen Sara E. Kalla Bo Yuan Jason H. Karnes Kimberly Walker Joshua D. Smith Sean McGee Aparna Radhakrishnan Andrew Haddad Philip E. Empey Qiaoyan Wang Lee Lichtenstein Diana Toledo Gail Jarvik Anjene Musick Richard A. Gibbs the All of Us Research Program Investigators The frequency of pathogenic variation in the All of Us cohort reveals ancestry-driven disparities Communications Biology |
| title | The frequency of pathogenic variation in the All of Us cohort reveals ancestry-driven disparities |
| title_full | The frequency of pathogenic variation in the All of Us cohort reveals ancestry-driven disparities |
| title_fullStr | The frequency of pathogenic variation in the All of Us cohort reveals ancestry-driven disparities |
| title_full_unstemmed | The frequency of pathogenic variation in the All of Us cohort reveals ancestry-driven disparities |
| title_short | The frequency of pathogenic variation in the All of Us cohort reveals ancestry-driven disparities |
| title_sort | frequency of pathogenic variation in the all of us cohort reveals ancestry driven disparities |
| url | https://doi.org/10.1038/s42003-023-05708-y |
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