Recall by genotype and cascade screening for familial hypercholesterolemia in a population-based biobank from Estonia
Purpose: Large-scale, population-based biobanks integrating health records and genomic profiles may provide a platform to identify individuals with disease-predisposing genetic variants. Here, we recall probands carrying familial hypercholesterolemia (FH)-associated variants, perform cascade screeni...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Springer Science and Business Media LLC
2020
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| Online Access: | https://hdl.handle.net/1721.1/125359 |
| _version_ | 1826209893093212160 |
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| author | Zekavat, Seyedeh M. Gabriel, Stacey Lander, Eric Steven Philippakis, Anthony A. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Zekavat, Seyedeh M. Gabriel, Stacey Lander, Eric Steven Philippakis, Anthony A. |
| author_sort | Zekavat, Seyedeh M. |
| collection | MIT |
| description | Purpose: Large-scale, population-based biobanks integrating health records and genomic profiles may provide a platform to identify individuals with disease-predisposing genetic variants. Here, we recall probands carrying familial hypercholesterolemia (FH)-associated variants, perform cascade screening of family members, and describe health outcomes affected by such a strategy. Methods: The Estonian Biobank of Estonian Genome Center, University of Tartu, comprises 52,274 individuals. Among 4776 participants with exome or genome sequences, we identified 27 individuals who carried FH-associated variants in the LDLR, APOB, or PCSK9 genes. Cascade screening of 64 family members identified an additional 20 carriers of FH-associated variants. Results: Via genetic counseling and clinical management of carriers, we were able to reclassify 51% of the study participants from having previously established nonspecific hypercholesterolemia to having FH and identify 32% who were completely unaware of harboring a high-risk disease-associated genetic variant. Imaging-based risk stratification targeted 86% of the variant carriers for statin treatment recommendations. Conclusion: Genotype-guided recall of probands and subsequent cascade screening for familial hypercholesterolemia is feasible within a population-based biobank and may facilitate more appropriate clinical management. |
| first_indexed | 2024-09-23T14:34:18Z |
| format | Article |
| id | mit-1721.1/125359 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T14:34:18Z |
| publishDate | 2020 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1253592022-10-01T21:43:58Z Recall by genotype and cascade screening for familial hypercholesterolemia in a population-based biobank from Estonia Zekavat, Seyedeh M. Gabriel, Stacey Lander, Eric Steven Philippakis, Anthony A. Massachusetts Institute of Technology. Department of Biology Purpose: Large-scale, population-based biobanks integrating health records and genomic profiles may provide a platform to identify individuals with disease-predisposing genetic variants. Here, we recall probands carrying familial hypercholesterolemia (FH)-associated variants, perform cascade screening of family members, and describe health outcomes affected by such a strategy. Methods: The Estonian Biobank of Estonian Genome Center, University of Tartu, comprises 52,274 individuals. Among 4776 participants with exome or genome sequences, we identified 27 individuals who carried FH-associated variants in the LDLR, APOB, or PCSK9 genes. Cascade screening of 64 family members identified an additional 20 carriers of FH-associated variants. Results: Via genetic counseling and clinical management of carriers, we were able to reclassify 51% of the study participants from having previously established nonspecific hypercholesterolemia to having FH and identify 32% who were completely unaware of harboring a high-risk disease-associated genetic variant. Imaging-based risk stratification targeted 86% of the variant carriers for statin treatment recommendations. Conclusion: Genotype-guided recall of probands and subsequent cascade screening for familial hypercholesterolemia is feasible within a population-based biobank and may facilitate more appropriate clinical management. European Union. Horizon 2020 Research and Innovation Programme (Grant 92145) European Regional Development Fund (2014-2020.4.01.15-0012 GENTRANSMED) National Institutes of Health (U.S.) (Grant R01 MP1GV17428) 2020-05-20T18:33:05Z 2020-05-20T18:33:05Z 2018-10 2020-01-22T18:49:12Z Article http://purl.org/eprint/type/JournalArticle 1098-3600 https://hdl.handle.net/1721.1/125359 Alver, Maris et al. “Recall by genotype and cascade screening for familial hypercholesterolemia in a population-based biobank from Estonia.” Genetics in medicine 21 (2019): 1173-1180 © 2019 The Author(s) en 10.1038/S41436-018-0311-2 Genetics in medicine Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Springer Science and Business Media LLC Nature |
| spellingShingle | Zekavat, Seyedeh M. Gabriel, Stacey Lander, Eric Steven Philippakis, Anthony A. Recall by genotype and cascade screening for familial hypercholesterolemia in a population-based biobank from Estonia |
| title | Recall by genotype and cascade screening for familial hypercholesterolemia in a population-based biobank from Estonia |
| title_full | Recall by genotype and cascade screening for familial hypercholesterolemia in a population-based biobank from Estonia |
| title_fullStr | Recall by genotype and cascade screening for familial hypercholesterolemia in a population-based biobank from Estonia |
| title_full_unstemmed | Recall by genotype and cascade screening for familial hypercholesterolemia in a population-based biobank from Estonia |
| title_short | Recall by genotype and cascade screening for familial hypercholesterolemia in a population-based biobank from Estonia |
| title_sort | recall by genotype and cascade screening for familial hypercholesterolemia in a population based biobank from estonia |
| url | https://hdl.handle.net/1721.1/125359 |
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