Analysis of Brugada syndrome loci reveals that fine-mapping clustered GWAS hits enhances the annotation of disease-relevant variants.

ABSTRACT: Genome-wide association studies (GWASs) are instrumental in identifying loci harboring common single-nucleotide variants (SNVs) that affect human traits and diseases. GWAS hits emerge in clusters, but the focus is often on the most significant hit in each trait- or disease-associated locus. The remaining hits represent SNVs in linkage disequilibrium (LD) and are considered redundant and thus frequently marginally reported or exploited. Here, we interrogate the value of integrating the full set of GWAS hits in a locus repeatedly associated with cardiac conduction traits and arrhythmia, SCN5A-SCN10A. Our analysis reveals 5 common 7-SNV haplotypes (Hap1-5) with 2 combinations associated with life-threatening arrhythmia-Brugada syndrome (the risk Hap^1/1 and protective

SUBMITTER: Pinsach-Abuin ML 

PROVIDER: S-EPMC8080235 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature