| Title | Identification of allele-specific KIV-2 repeats and impact on Lp(a) measurements for cardiovascular disease risk. |
| Publication Type | Journal Article |
| Year of Publication | 2024 |
| Authors | Behera, S, Belyeu, JR, Chen, X, Paulin, LF, Nguyen, NQuynh H, Newman, E, Mahmoud, M, Menon, VK, Qi, Q, Joshi, P, Marcovina, S, Rossi, M, Roller, E, Han, J, Onuchic, V, Avery, CL, Ballantyne, CM, Rodriguez, CJ, Kaplan, RC, Muzny, DM, Metcalf, GA, Gibbs, RA, Yu, B, Boerwinkle, E, Eberle, MA, Sedlazeck, FJ |
| Journal | BMC Med Genomics |
| Volume | 17 |
| Issue | 1 |
| Pagination | 255 |
| Date Published | 2024 Oct 24 |
| ISSN | 1755-8794 |
| Keywords | Alleles, Cardiovascular Diseases, DNA Copy Number Variations, Genetic Predisposition to Disease, Humans, Lipoprotein(a), Polymorphism, Single Nucleotide |
| 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. |
| DOI | 10.1186/s12920-024-02024-0 |
| Alternate Journal | BMC Med Genomics |
| PubMed ID | 39449055 |
| PubMed Central ID | PMC11515395 |