Publication Date
10-24-2024
Journal
BMC Medical Genomics
DOI
10.1186/s12920-024-02024-0
PMID
39449055
PMCID
PMC11515395
PubMedCentral® Posted Date
10-24-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Humans, Cardiovascular Diseases, Alleles, Lipoprotein(a), DNA Copy Number Variations, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, LPA, Copy number variation, Cardiovascular disease, Next Generation Sequencing, Illumina
Abstract
The abundance of Lp(a) protein holds significant implications for the risk of cardiovascular disease (CVD), which is directly impacted by the copy number (CN) of KIV-2, a 5.5 kbp sub-region. KIV-2 is highly polymorphic in the population and accurate analysis is challenging. In this study, we present the DRAGEN KIV-2 CN caller, which utilizes short reads. Data across 166 WGS show that the caller has high accuracy, compared to optical mapping and can further phase approximately 50% of the samples. We compared KIV-2 CN numbers to 24 previously postulated KIV-2 relevant SNVs, revealing that many are ineffective predictors of KIV-2 copy number. Population studies, including USA-based cohorts, showed distinct KIV-2 CN, distributions for European-, African-, and Hispanic-American populations and further underscored the limitations of SNV predictors. We demonstrate that the CN estimates correlate significantly with the available Lp(a) protein levels and that phasing is highly important.
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Biological Phenomena, Cell Phenomena, and Immunity Commons, Biomedical Informatics Commons, Genetics and Genomics Commons, Medical Genetics Commons, Medical Molecular Biology Commons, Medical Specialties Commons
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