ArticleNature communications2018
Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries.
Erratum issuedOpen access · goldAbstract read
In one paragraph
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 67 papers, 4 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed, 4 pooled it
9.9field-weighted citation impact, top 2% of its field
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
67 citing papers in PubMed, 4 syntheses or guidelines pooled it, 109 citations in OpenAlex.
- Major Facilitator Superfamily Domain Containing 5 Inhibition Reduces Lipoprotein(a) Uptake and Calcification in Valvular Heart Disease.Circulation · 2024Pooled it
- The Effect of Bariatric Surgery on Circulating Levels of Lipoprotein (a): A Meta-analysis.BioMed research international · 2022Pooled it
- Genome-Wide Association Study HighlightsArteriosclerosis, thrombosis, and vascular biology · 2021Pooled it
- Genetic Variation in LPA, Calcific Aortic Valve Stenosis in Patients Undergoing Cardiac Surgery, and Familial Risk of Aortic Valve Microcalcification.JAMA cardiology · 2019Pooled it
- Article
- Baseline self-reported supplement category use and two-visit difference in lipoprotein(a): an observational analysis in UK Biobank.Lipids in health and disease · 2026Observational
- Genetic Prediction of Circulating Lipoprotein(a) Levels in Diverse Populations.medRxiv : the preprint server for health sciences · 2026Article
- Family history of premature atherosclerotic cardiovascular disease and lipoprotein(a) levels: a multicohort analysis.European journal of preventive cardiology · 2026Article
- Replication stress increases de novo CNVs across the malaria parasite genome.Nucleic acids research · 2026Article
- Lp(a) in the Horizon of Diagnostics and Therapy.International journal of molecular sciences · 2025Review
- Ancestral Variation in Lp(a): Epidemiology, Isoform Diversity, and Testing.Current atherosclerosis reports · 2025Review
- Novel Method for Predicting Lp(a) From Genomic Testing Identifies ASCVD Risk Across a Diverse Cohort.JACC. Basic to translational science · 2025Article
- Replication stress increases de novo CNVs across the malaria parasite genome.bioRxiv : the preprint server for biology · 2025Article
- Lipoprotein (a) in primary cardiovascular disease prevention is actionable today.American heart journal plus : cardiology research and practice · 2025Review
- Genetic Risk Profiles for Atherosclerosis and Venous Thromboembolism in Azorean and Mainland Portuguese Populations: A Comparative Analysis.Current issues in molecular biology · 2025Article
- Association of Lipoprotein A rs10455872 Polymorphism with Childhood Obesity and Obesity-Related Outcomes.Diagnostics (Basel, Switzerland) · 2025Article
- Polygenic and pharmacogenomic contributions to medication dosing: a real-world longitudinal biobank study.Journal of translational medicine · 2025Article
- Functional interrogation of cellular Lp(a) uptake by genome-scale CRISPR screening.Atherosclerosis · 2025Article
- Serum Lipids, Inflammation, and the Risk of Atrial Fibrillation: Pathophysiological Links and Clinical Evidence.Journal of clinical medicine · 2025Review
- 2025 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association.Circulation · 2025Review
7 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
- Erratum issued
Authors and funding
39 authors at 20 institutions in 5 countries.
Seyedeh M ZekavatProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.ORCID http://orcid.org/0000-0003-4026-8944
Sanni RuotsalainenInstitute for Molecular Medicine, University of Helsinki, Helsinki, Finland.
Robert E HandsakerProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.ORCID http://orcid.org/0000-0002-3128-3547
Maris AlverDepartment of Biotechnology, Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
Jonathan BloomProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.ORCID http://orcid.org/0000-0001-8497-1434
Timothy PoterbaProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Cotton SeedProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Jason ErnstDepartment of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA, 90095, USA.ORCID http://orcid.org/0000-0003-4026-7853
Mark ChaffinProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Jesse EngreitzProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.ORCID http://orcid.org/0000-0002-5754-1719
Gina M PelosoDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, 02118, USA.
Ani ManichaikulCenter for Public Health Genomics, University of Virginia, Charlottesville, VA, 22904, USA.
Chaojie YangCenter for Public Health Genomics, University of Virginia, Charlottesville, VA, 22904, USA.
Kathleen A RyanProgram in Personalized and Genomic Medicine, Division of Endocrinology, Diabetes & Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Mao FuProgram in Personalized and Genomic Medicine, Division of Endocrinology, Diabetes & Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
W Craig JohnsonDepartment of Biostatistics, School of Public Health and Community Medicine, University of Washington, Seattle, WA, 98195, USA.
Michael TsaiDepartment of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, 55455, USA.
Matthew BudoffDivision of Cardiology, Harbor-UCLA Medical Center, Los Angeles Biomedical Research Institute, Los Angeles, CA, 90509, USA.
Ramachandran S VasanNHLBI Framingham Heart Study, Framingham, MA, 20892, USA.
L Adrienne CupplesDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, 02118, USA.
Jerome I RotterDepartments of Pediatrics and Medicine, The Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, CA, 90509, USA.
Stephen S RichCenter for Public Health Genomics, University of Virginia, Charlottesville, VA, 22904, USA.
Wendy PostDivision of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Braxton D MitchellDepartment of Medicine, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Adolfo CorreaDepartment of Medicine, University of Mississippi Medical Center, Jackson, MS, 39216, USA.ORCID http://orcid.org/0000-0002-9501-600X
Andres MetspaluEstonian Genome Center, Tallinn, Estonia.
James G WilsonDepartment of Medicine, University of Mississippi Medical Center, Jackson, MS, 39216, USA.
Veikko SalomaaNational Institute for Health and Welfare, Helsinki, Finland.
Manolis KellisProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Mark J DalyProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Benjamin M NealeProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.ORCID http://orcid.org/0000-0003-1513-6077
Steven McCarrollProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Ida SurakkaInstitute for Molecular Medicine, University of Helsinki, Helsinki, Finland.
Tonu EskoProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.ORCID http://orcid.org/0000-0003-1982-6569
Andrea GannaProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Samuli RipattiProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Sekar KathiresanProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA. skathiresan1@mgh.harvard.edu.ORCID http://orcid.org/0000-0002-6724-032X
Pradeep NatarajanProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA. pnatarajan@mgh.harvard.edu.ORCID http://orcid.org/0000-0001-8402-7435
NHLBI TOPMed Lipids Working Group
University of Washington · USUniversity of Maryland, Baltimore · USUniversity of Michigan · USBroad Institute · USBrigham and Women's Hospital · USJohns Hopkins University · USUniversity of Colorado Denver · USNational Institutes of Health · USUniversity of Mississippi · USUniversity of Virginia · USIcahn School of Medicine at Mount Sinai · USNational Jewish Health · USNew York Genome Center · USThe Lundquist Institute · USThe University of Texas Rio Grande Valley · USWashington University in St. Louis · USBoston University · USMassachusetts General Hospital · USStanford University · USUniversity of Alabama at Birmingham · US
Funding
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007205 · NIGMS · YALE UNIVERSITY · PI KAZMIERCZAK, BARBARA I · 1985 to 2019
$42.9MTracking and Evaluation CoreU54GM115428 · NIGMS · UNIVERSITY OF MISSISSIPPI MED CTR · PI COMPRETTA, CAROLINE E. · 2016 to 2025
$38.2MRole of obesity in preeclamptic pregnancy.P20GM121334 · NIGMS · UNIVERSITY OF MISSISSIPPI MED CTR · PI Jane F Reckelhoff · 2017 to 2026
$26.4MCell Interactions in the Inflamed Intestinal MucosaR01DK075787 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI JOEL N HIRSCHHORN · 2007 to 2026
$13.1MA Family-based Exome Sequencing Approach to Identify Platelet Aggregation GenesR01HL112064 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI MATHIAS, RASIKA ANN · 2012 to 2015
$5.1MWhole genome sequences in individuals to comprehensively characterize the genetic mechanisms of dyslipidemiasR01HL142711 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI Satoshi Koyama, Gina Marie Peloso · 2019 to 2026
$4.7MNatural Genetic Variation in the Human GenomeR01HG002898 · NHGRI · UNIVERSITY OF MARYLAND BALTIMORE · PI DEVINE, SCOTT E · 2004 to 2019
$3.7MDeciphering the genetic mechanisms of atrial fibrillationR01HL138737 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI DARBAR, DAWOOD · 2017 to 2020
$2.6MDNA methylation markers of Multimorbidity in Aging Humans and MiceK01AG059898 · NIA · UNIVERSITY OF WASHINGTON · PI SALIMI, SHABNAM · 2019 to 2023
$613kEpigenomics of Cardiometabolic Diseases in Mexican AmericansK01HL130609 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI HIDALGO, BERTHA · 2016 to 2019
$568kUnderstanding modifiers of mendelian mutation penetrance using familial hypercholesterolemia as a modelK08HL140203 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI NATARAJAN, PRADEEP · 2018 to 2019
$343kNHGRI NIH HHS R01 HG002898NHLBI NIH HHS K01 HL130609NHLBI NIH HHS K08 HL140203NHLBI NIH HHS R01 HL112064NHLBI NIH HHS R01 HL138737NHLBI NIH HHS R01 HL142711NIA NIH HHS K01 AG059898NIDDK NIH HHS R01 DK075787NIGMS NIH HHS P20 GM121334NIGMS NIH HHS T32 GM007205NIGMS NIH HHS U54 GM115428
Abstract
Lipoprotein(a), Lp(a), is a modified low-density lipoprotein particle that contains apolipoprotein(a), encoded by LPA, and is a highly heritable, causal risk factor for cardiovascular diseases that varies in concentrations across ancestries. Here, we use deep-coverage whole genome sequencing in 8392 individuals of European and African ancestry to discover and interpret both single-nucleotide variants and copy number (CN) variation associated with Lp(a). We observe that genetic determinants between Europeans and Africans have several unique determinants. The common variant rs12740374 associated with Lp(a) cholesterol is an eQTL for SORT1 and independent of LDL cholesterol. Observed associations of aggregates of rare non-coding variants are largely explained by LPA structural variation, namely the LPA kringle IV 2 (KIV2)-CN. Finally, we find that LPA risk genotypes confer greater relative risk for incident atherosclerotic cardiovascular diseases compared to directly measured Lp(a), and are significantly associated with measures of subclinical atherosclerosis in African Americans.
Indexed as
DNA Copy Number VariationsGenome, HumanPolymorphism, Single NucleotideAdaptor Proteins, Vesicular TransportBlack or African AmericanBlack PeopleCardiovascular DiseasesCholesterol, LDLGene ExpressionGenome-Wide Association StudyHumansLipoprotein(a)Quantitative Trait LociRisk FactorsSortilinWhite PeopleAdaptor Proteins, Vesicular TransportCholesterol, LDLLipoprotein(a)Sortilin
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