SCN5A Mutation Type and a Genetic Risk Score Associate Variably With Brugada Syndrome Phenotype in SCN5A Families
Why the study?
Incomplete penetrance and genotype-negative phenotype-positive individuals are observed in SCN5A-associated Brugada syndrome families.
Does a Brugada syndrome genetic risk score associate with the Brugada syndrome phenotype in SCN5A families?
Population
312 subjects from cohorts harboring SCN5A mutations recruited from 16 centers
Comparison
BrS-GRS and SCN5A mutation type
Design
Multicenter observational cohort study
Authors
Discussion
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Member takes
Implication
BrS-GRS associates with phenotype expressivity in SCN5A families; hypothesis-generating for polygenic modifiers and requires prospective validation.
Structured PICO
Does a Brugada syndrome genetic risk score associate with the Brugada syndrome phenotype in SCN5A families?
P
Population
312 subjects with a spontaneous type 1 Brugada ECG pattern or positive/negative drug challenge from cohorts harboring SCN5A mutations, recruited from 16 centers.
I
Intervention
Brugada syndrome genetic risk score (BrS-GRS) ≥4 risk alleles and SCN5A mutation type
C
Comparator
BrS-GRS <4 risk alleles
O
Outcome
Brugada syndrome phenotypesurrogate
Common genetic variation (BrS-GRS) is associated with variable expressivity of the Brugada syndrome phenotype in SCN5A families, helping explain incomplete penetrance.
Cite This Study
Wijeyeratne et al. (2020) studied this question.