Identification of allele-specific KIV-2 repeats and impact on Lp(a) measurements for cardiovascular disease risk
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, w...
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2024-10-01
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| Series: | BMC Medical Genomics |
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| Online Access: | https://doi.org/10.1186/s12920-024-02024-0 |
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| author | Sairam Behera Jonathan R. Belyeu Xiao Chen Luis F. Paulin Ngoc Quynh H. Nguyen Emma Newman Medhat Mahmoud Vipin K. Menon Qibin Qi Parag Joshi Santica Marcovina Massimiliano Rossi Eric Roller James Han Vitor Onuchic Christy L. Avery Christie M. Ballantyne Carlos J. Rodriguez Robert C. Kaplan Donna M. Muzny Ginger A. Metcalf Richard A. Gibbs Bing Yu Eric Boerwinkle Michael A. Eberle Fritz J. Sedlazeck |
| author_facet | Sairam Behera Jonathan R. Belyeu Xiao Chen Luis F. Paulin Ngoc Quynh H. Nguyen Emma Newman Medhat Mahmoud Vipin K. Menon Qibin Qi Parag Joshi Santica Marcovina Massimiliano Rossi Eric Roller James Han Vitor Onuchic Christy L. Avery Christie M. Ballantyne Carlos J. Rodriguez Robert C. Kaplan Donna M. Muzny Ginger A. Metcalf Richard A. Gibbs Bing Yu Eric Boerwinkle Michael A. Eberle Fritz J. Sedlazeck |
| author_sort | Sairam Behera |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-b08e11c0c6a64b4e840870232441e2bd |
| institution | Kabale University |
| issn | 1755-8794 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medical Genomics |
| spelling | doaj-art-b08e11c0c6a64b4e840870232441e2bd2024-11-17T12:53:04ZengBMCBMC Medical Genomics1755-87942024-10-0117111510.1186/s12920-024-02024-0Identification of allele-specific KIV-2 repeats and impact on Lp(a) measurements for cardiovascular disease riskSairam Behera0Jonathan R. Belyeu1Xiao Chen2Luis F. Paulin3Ngoc Quynh H. Nguyen4Emma Newman5Medhat Mahmoud6Vipin K. Menon7Qibin Qi8Parag Joshi9Santica Marcovina10Massimiliano Rossi11Eric Roller12James Han13Vitor Onuchic14Christy L. Avery15Christie M. Ballantyne16Carlos J. Rodriguez17Robert C. Kaplan18Donna M. Muzny19Ginger A. Metcalf20Richard A. Gibbs21Bing Yu22Eric Boerwinkle23Michael A. Eberle24Fritz J. Sedlazeck25Human Genome Sequencing Center, Baylor College of MedicineIllumina IncIllumina IncHuman Genome Sequencing Center, Baylor College of MedicineSchool of Public Health, University of Texas Health Science CenterIllumina IncHuman Genome Sequencing Center, Baylor College of MedicineHuman Genome Sequencing Center, Baylor College of MedicineDepartment of Epidemiology and Population Health, Albert Einstein College of MedicineMedpace Reference LaboratoriesUniversity of Texas Southwestern Medical CenterIllumina IncIllumina IncIllumina IncIllumina IncDepartment of Epidemiology, University of North Carolina at Chapel HillDepartment of Medicine, Baylor College of MedicineDepartment of Epidemiology and Population Health, Albert Einstein College of MedicineDepartment of Epidemiology and Population Health, Albert Einstein College of MedicineHuman Genome Sequencing Center, Baylor College of MedicineHuman Genome Sequencing Center, Baylor College of MedicineHuman Genome Sequencing Center, Baylor College of MedicineSchool of Public Health, University of Texas Health Science CenterHuman Genome Sequencing Center, Baylor College of MedicineIllumina IncHuman Genome Sequencing Center, Baylor College of MedicineAbstract 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.https://doi.org/10.1186/s12920-024-02024-0LPACopy number variationCardiovascular diseaseNext Generation SequencingIllumina |
| spellingShingle | Sairam Behera Jonathan R. Belyeu Xiao Chen Luis F. Paulin Ngoc Quynh H. Nguyen Emma Newman Medhat Mahmoud Vipin K. Menon Qibin Qi Parag Joshi Santica Marcovina Massimiliano Rossi Eric Roller James Han Vitor Onuchic Christy L. Avery Christie M. Ballantyne Carlos J. Rodriguez Robert C. Kaplan Donna M. Muzny Ginger A. Metcalf Richard A. Gibbs Bing Yu Eric Boerwinkle Michael A. Eberle Fritz J. Sedlazeck Identification of allele-specific KIV-2 repeats and impact on Lp(a) measurements for cardiovascular disease risk BMC Medical Genomics LPA Copy number variation Cardiovascular disease Next Generation Sequencing Illumina |
| title | Identification of allele-specific KIV-2 repeats and impact on Lp(a) measurements for cardiovascular disease risk |
| title_full | Identification of allele-specific KIV-2 repeats and impact on Lp(a) measurements for cardiovascular disease risk |
| title_fullStr | Identification of allele-specific KIV-2 repeats and impact on Lp(a) measurements for cardiovascular disease risk |
| title_full_unstemmed | Identification of allele-specific KIV-2 repeats and impact on Lp(a) measurements for cardiovascular disease risk |
| title_short | Identification of allele-specific KIV-2 repeats and impact on Lp(a) measurements for cardiovascular disease risk |
| title_sort | identification of allele specific kiv 2 repeats and impact on lp a measurements for cardiovascular disease risk |
| topic | LPA Copy number variation Cardiovascular disease Next Generation Sequencing Illumina |
| url | https://doi.org/10.1186/s12920-024-02024-0 |
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