Recall by genotype and cascade screening for familial hypercholesterolemia in a population-based biobank from Estonia.

Genet Med
Authors
Keywords
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
Journal
Genet Med
Volume
21
Issue
5
Pages
1173-1180
Date Published
2019 05
ISSN
1530-0366
DOI
10.1038/s41436-018-0311-2
PubMed ID
30270359
PubMed Central ID
PMC6443485
Links
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
Additional Materials