Recall by genotype and cascade screening for familial hypercholesterolemia in a population-based biobank from Estonia.
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Abstract | 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. |
Year of Publication | 2019
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Journal | Genet Med
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Volume | 21
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Issue | 5
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Pages | 1173-1180
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Date Published | 2019 05
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ISSN | 1530-0366
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DOI | 10.1038/s41436-018-0311-2
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PubMed ID | 30270359
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PubMed Central ID | PMC6443485
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Grant list | K08 HL140203 / HL / NHLBI NIH HHS / United States
R01 DK075787 / DK / NIDDK NIH HHS / United States
R01 HL142711 / HL / NHLBI NIH HHS / United States
T32 GM007205 / GM / NIGMS NIH HHS / United States
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