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鉴定等位基因特异性 KIV-2 重复序列及其对心血管疾病风险的 Lp(a)测量的影响。

Identification of allele-specific KIV-2 repeats and impact on Lp(a) measurements for cardiovascular disease risk.

机构信息

Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.

Illumina Inc, San Diego, CA, USA.

出版信息

BMC Med Genomics. 2024 Oct 24;17(1):255. doi: 10.1186/s12920-024-02024-0.

DOI:10.1186/s12920-024-02024-0
PMID:39449055
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11515395/
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.

摘要

载脂蛋白(a)蛋白的丰度对心血管疾病(CVD)的风险具有重要意义，而载脂蛋白(a)蛋白的拷贝数(CN)又直接受到 KIV-2 的影响，KIV-2 是一个 5.5kbp 的亚区。KIV-2 在人群中高度多态性，准确分析具有挑战性。在这项研究中，我们提出了 DRAGEN KIV-2 CN 调用器，它利用短读长。来自 166 个 WGS 的数据表明，与光学作图相比，该调用器具有很高的准确性，并且可以进一步对大约 50%的样本进行相位分析。我们将 KIV-2 CN 数量与 24 个先前假设的 KIV-2 相关 SNV 进行了比较，结果表明，许多 SNV 并不能有效预测 KIV-2 的拷贝数。包括美国队列在内的人群研究表明，欧洲人、非洲人和西班牙裔美国人的 KIV-2 CN 分布明显不同，进一步强调了 SNV 预测的局限性。我们证明了 CN 估计与可用的载脂蛋白(a)蛋白水平显著相关，并且相位分析非常重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a626/11515395/0d5ff0cd9097/12920_2024_2024_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a626/11515395/92796ebcc4dc/12920_2024_2024_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a626/11515395/98dce60fa7cd/12920_2024_2024_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a626/11515395/58789a48be94/12920_2024_2024_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a626/11515395/24557fc16938/12920_2024_2024_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a626/11515395/66befc53ea7f/12920_2024_2024_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a626/11515395/0d5ff0cd9097/12920_2024_2024_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a626/11515395/92796ebcc4dc/12920_2024_2024_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a626/11515395/98dce60fa7cd/12920_2024_2024_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a626/11515395/58789a48be94/12920_2024_2024_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a626/11515395/24557fc16938/12920_2024_2024_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a626/11515395/66befc53ea7f/12920_2024_2024_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a626/11515395/0d5ff0cd9097/12920_2024_2024_Fig6_HTML.jpg

相似文献

[1]
Identification of allele-specific KIV-2 repeats and impact on Lp(a) measurements for cardiovascular disease risk.

BMC Med Genomics. 2024-10-24

[2]
Identification of allele-specific KIV-2 repeats and impact on Lp(a) measurements for cardiovascular disease risk.

bioRxiv. 2023-4-27

[3]
Sequence variation within the KIV-2 copy number polymorphism of the human LPA gene in African, Asian, and European populations.

PLoS One. 2015-3-30

[4]
A novel but frequent variant in LPA KIV-2 is associated with a pronounced Lp(a) and cardiovascular risk reduction.

Eur Heart J. 2017-6-14

[5]
Nanopore sequencing with unique molecular identifiers enables accurate mutation analysis and haplotyping in the complex lipoprotein(a) KIV-2 VNTR.

Genome Med. 2024-10-8

[6]
Lipoprotein(a) and apolipoprotein(a) isoform size: Associations with angiographic extent and severity of coronary artery disease, and carotid artery plaque.

Atherosclerosis. 2018-6-18

[7]
Low LPA gene kringle IV-2 repeat copy number association with elevated lipoprotein (a) concentration as an independent risk factor of coronary atherosclerotic heart disease in the Chinese Han population.

Lipids Health Dis. 2018-5-10

[8]
kringle IV type 2 is associated with type 2 diabetes in a Chinese population with very high cardiovascular risk.

J Lipid Res. 2018-3-6

[9]
Apolipoprotein(a) Kringle-IV Type 2 Copy Number Variation Is Associated with Venous Thromboembolism.

PLoS One. 2016-2-22

[10]
Comprehensive analysis of genomic variation in the LPA locus and its relationship to plasma lipoprotein(a) in South Asians, Chinese, and European Caucasians.

Circ Cardiovasc Genet. 2010-2

引用本文的文献

[1]
Cardiovascular Implications of Lipoprotein(a) and its Genetic Variants: A Critical Review From the Middle East.

JACC Asia. 2025-7

[2]
KILDA: identifying KIV-2 repeats from kmers.

NAR Genom Bioinform. 2025-5-30

[3]
A Hitchhiker's Guide to long-read genomic analysis.

Genome Res. 2025-4-14

[4]
GREGoR: Accelerating Genomics for Rare Diseases.

ArXiv. 2024-12-18

[5]
Comprehensive genome analysis and variant detection at scale using DRAGEN.

Nat Biotechnol. 2024-10-25

[6]
Closing the gap: Solving complex medically relevant genes at scale.

medRxiv. 2024-3-18

本文引用的文献

[1]
Lipoprotein(a) beyond the kringle IV repeat polymorphism: The complexity of genetic variation in the LPA gene.

Atherosclerosis. 2022-5

[2]
Associations of combined lifestyle and genetic risks with incident psoriasis: A prospective cohort study among UK Biobank participants of European ancestry.

J Am Acad Dermatol. 2022-8

[3]
Segmental duplications and their variation in a complete human genome.

Science. 2022-4

[4]
Protein-coding repeat polymorphisms strongly shape diverse human phenotypes.

Science. 2021-9-24

[5]
Genetic testing in ambulatory cardiology clinics reveals high rate of findings with clinical management implications.

Genet Med. 2021-12

[6]
The ARIC (Atherosclerosis Risk In Communities) Study: JACC Focus Seminar 3/8.

J Am Coll Cardiol. 2021-6-15

[7]
Haplotype-resolved diverse human genomes and integrated analysis of structural variation.

Science. 2021-4-2

[8]
Clinical Utility of Lipoprotein(a) and LPA Genetic Risk Score in Risk Prediction of Incident Atherosclerotic Cardiovascular Disease.

JAMA Cardiol. 2021-3-1

[9]
Investigation of a nonsense mutation located in the complex KIV-2 copy number variation region of apolipoprotein(a) in 10,910 individuals.

Genome Med. 2020-8-21

[10]
Spinal muscular atrophy diagnosis and carrier screening from genome sequencing data.

Genet Med. 2020-5

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