Discordant calls across genotype discovery approaches elucidate variants with systematic errors.

ABSTRACT: Large-scale high-throughput sequencing data sets have been transformative for informing clinical variant interpretation and for use as reference panels for statistical and population genetic efforts. Although such resources are often treated as ground truth, we find that in widely used reference data sets such as the Genome Aggregation Database (gnomAD), some variants pass gold-standard filters, yet are systematically different in their genotype calls across genotype discovery approaches. The inclusion of such discordant sites in study designs involving multiple genotype discovery strategies could bias results and lead to false-positive hits in association studies owing to technological artifacts rather than a true relationship to the phenotype. Here, we describe this phenomenon of discord

SUBMITTER: Atkinson EG 

PROVIDER: S-EPMC10519400 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature