Evidence map›Paper›PMID 28007139›Full record

ArticleJournal of the American College of Cardiology2016

Phenotypic Characterization of Genetically Lowered Human Lipoprotein(a) Levels.

Connor A Emdin, Amit V Khera, Pradeep Natarajan, Derek Klarin, Hong-Hee Won, Gina M Peloso, Nathan O Stitziel, Akihiro Nomura, Seyedeh M Zekavat, Alexander G Bick and 30 more

Open access · greenAbstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of the American College of Cardiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
121citing papers in PubMed, 6 pooled it
23.9field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

121 citing papers in PubMed, 6 syntheses or guidelines pooled it, 249 citations in OpenAlex.

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  15. Clinical utility of polygenic risk scores in cardiovascular disorders.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2026
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61 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

40 authors at 18 institutions in 8 countries.

Connor A EmdinCenter for Human Genetic Research, Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts.
Amit V KheraCenter for Human Genetic Research, Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts.
Pradeep NatarajanCenter for Human Genetic Research, Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts.
Derek KlarinCenter for Human Genetic Research, Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts.
Hong-Hee WonSamsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Samsung Medical Center, Seoul, Republic of Korea.
Gina M PelosoProgram in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts; Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts.
Nathan O StitzielDepartments of Medicine, Genetics, and the McDonnell Genome Institute, Washington University School of Medicine, St. Louis, Missouri.
Akihiro NomuraCenter for Human Genetic Research, Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts.
Seyedeh M ZekavatCenter for Human Genetic Research, Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts.
Alexander G BickProgram in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts.
Namrata GuptaProgram in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts.
Rosanna AsseltaDepartment of Biomedical Sciences, Humanitas University and Humanitas Clinical and Research Center, Milan, Italy.
Stefano DugaDepartment of Biomedical Sciences, Humanitas University and Humanitas Clinical and Research Center, Milan, Italy.
Piera Angelica MerliniOspedale Niguarda, Milan, Italy.
Adolfo CorreaJackson Heart Study, Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi.
Thorsten KesslerDeutsches Herzzentrum München, Technische Universität München, Deutsches Zentrum für Herz-Kreislauf-Forschung, München, Germany; Munich Heart Alliance, München, Germany.
James G WilsonDepartment of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi.
Matthew J BownDepartments of Cardiovascular Sciences and NIHR Leicester Cardiovascular Biomedical Research Unit, University of Leicester, Leicester, United Kingdom.
Alistair S HallLeeds Institute of Cardiovascular and Metabolic Medicine, Leeds University, Leeds, United Kingdom.
Peter S BraundDepartments of Cardiovascular Sciences and NIHR Leicester Cardiovascular Biomedical Research Unit, University of Leicester, Leicester, United Kingdom.
Nilesh J SamaniDepartments of Cardiovascular Sciences and NIHR Leicester Cardiovascular Biomedical Research Unit, University of Leicester, Leicester, United Kingdom.
Heribert SchunkertDeutsches Herzzentrum München, Technische Universität München, Deutsches Zentrum für Herz-Kreislauf-Forschung, München, Germany.
Jaume MarrugatCardiovascular Epidemiology & Genetics, IMIM (Hospital del Mar Research Institute), Barcelona, Spain.
Roberto ElosuaCardiovascular Epidemiology & Genetics, IMIM (Hospital del Mar Research Institute), Barcelona, Spain.
Ruth McPhersonUniversity of Ottawa Heart Institute, Ottawa, Ontario, Canada.
Martin FarrallDivision of Cardiovascular Medicine, Radcliffe Department of Medicine and the Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
Hugh WatkinsDivision of Cardiovascular Medicine, Radcliffe Department of Medicine and the Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
Cristen WillerDepartment of Computational Medicine and Bioinformatics, Department of Human Genetics, and Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
Gonçalo R AbecasisCenter for Statistical Genetics, Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan.
Janine F FelixDepartment of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Ramachandran S VasanNational Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, Massachusetts; Sections of Cardiology, Preventive Medicine and Epidemiology, Department of Medicine, Boston University Schools of Medicine and Public Health, Boston, Massachusetts.
Eric LanderProgram in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts.
Daniel J RaderDepartment of Genetics, University of Pennsylvania, Philadelphia, Pennsylvania.
John DaneshPublic Health and Primary Care, University of Cambridge, Cambridge, United Kingdom; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom; National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
Diego ArdissinoDivision of Cardiology, Azienda Ospedaliero-Universitaria di Parma, University of Parma, Parma, Italy; ASTC: Associazione per lo Studio Della Trombosi in Cardiologia, Pavia, Italy.
Stacey GabrielProgram in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts.
Danish SaleheenBiostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Sekar KathiresanCenter for Human Genetic Research, Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts. Electronic address: skathiresan1@mgh.harvard.edu.
CHARGE–Heart Failure Consortium
CARDIoGRAM Exome Consortium
Broad Institute · USUniversity of Leicester · GBCentre for Human Genetics · GBGerman Centre for Cardiovascular Research · DEHospital Del Mar · ESHumanitas University · ITJackson Memorial Hospital · USUniversity of Michigan · USUniversity of Pennsylvania · USAzienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda · ITErasmus MC · NLFramingham Heart Study · USJames S. McDonnell Foundation · USOspedale di Parma · ITSamsung Medical Center · KRUniversity of Leeds · GBUniversity of Ottawa · CAWellcome Sanger Institute · GB

Funding

Large Scale Sequencing and Analysis of GenomesU54HG003067 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GABRIEL, STACEY, LANDER, ERIC S · 2004 to 2015
$568.6M
Northwest Genomics CenterRC2HL102926 · NHLBI · UNIVERSITY OF WASHINGTON · PI GREEN, PHILIP P, NICKERSON, DEBORAH A · 2009 to 2009
$11.0M
HARVARD-LONGWOOD RESEARCH TRAINING IN VASCULAR SURGERYT32HL007734 · NHLBI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI FERRAN, CHRISTIANE, LOGERFO, FRANK W · 1993 to 2023
$10.5M
Comprehensive Sequencing and Analysis of Variation in NHLBI CohortsRC2HL102925 · NHLBI · BROAD INSTITUTE, INC. · PI ALTSHULER, DAVID, GABRIEL, STACEY · 2009 to 2009
$10.2M
Harvard Clinical and Translational Science CenterKL2TR001100 · NCATS · HARVARD MEDICAL SCHOOL · PI NADLER, LEE MARSHALL · 2013 to 2017
$8.5M
Using genetic variation to study biology of blood lipids & coronary heart diseaseR01HL127564 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Pradeep Natarajan, Gina Marie Peloso · 2015 to 2026
$7.3M
ANGPTL3 DEFICIENCY AND ATHEROSCLEROSIS IN HUMANSR01HL131961 · NHLBI · WASHINGTON UNIVERSITY · PI STITZIEL, NATHAN OLIVER · 2016 to 2020
$3.2M
ARRA - NHLBI Lung Cohorts Sequencing ProjectRC2HL102923 · NHLBI · UNIVERSITY OF WASHINGTON · PI BAMSHAD, MICHAEL JOSEPH, BARNES, KATHLEEN C · 2009 to 2009
$2.6M
WHI Sequencing Project (WHISP)RC2HL102924 · NHLBI · OHIO STATE UNIVERSITY · PI CARLSON, CHRISTOPHER S, JACKSON, REBECCA D · 2009 to 2009
$2.1M
Human Exome Sequencing in Six Well-Phenotyped NHLBI CohortsRC2HL103010 · NHLBI · UNIVERSITY OF VIRGINIA · PI RICH, STEPHEN S. · 2009 to 2009
$817k
Rare coding variation and risk for myocardial infarctionK08HL114642 · NHLBI · WASHINGTON UNIVERSITY · PI STITZIEL, NATHAN OLIVER · 2012 to 2016
$703k
Discovering lipoprotein lipase pathway variants that protect against CHDK01HL125751 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI PELOSO, GINA MARIE · 2015 to 2018
$562k
British Heart Foundation CS/14/2/30841British Heart Foundation RG/13/13/30194Medical Research Council MC_QA137853Medical Research Council MR/L003120/1NCATS NIH HHS KL2 TR001100NHGRI NIH HHS U54 HG003067NHLBI NIH HHS K01 HL125751NHLBI NIH HHS K08 HL114642NHLBI NIH HHS R01 HL127564NHLBI NIH HHS R01 HL131961NHLBI NIH HHS RC2 HL102923NHLBI NIH HHS RC2 HL102924NHLBI NIH HHS RC2 HL102925NHLBI NIH HHS RC2 HL102926NHLBI NIH HHS RC2 HL103010NHLBI NIH HHS T32 HL007734
6 · The paper itself

Abstract

backgroundGenomic analyses have suggested that the LPA gene and its associated plasma biomarker, lipoprotein(a) (Lp[a]), represent a causal risk factor for coronary heart disease (CHD). As such, lowering Lp(a) levels has emerged as a therapeutic strategy. Beyond target identification, human genetics may contribute to the development of new therapies by defining the full spectrum of beneficial and adverse consequences and by developing a dose-response curve of target perturbation.

objectivesThe goal of this study was to establish the full phenotypic impact of LPA gene variation and to estimate a dose-response curve between genetically altered plasma Lp(a) and risk for CHD.

methodsWe leveraged genetic variants at the LPA gene from 3 data sources: individual-level data from 112,338 participants in the U.K. Biobank; summary association results from large-scale genome-wide association studies; and LPA gene sequencing results from case subjects with CHD and control subjects free of CHD.

resultsOne SD genetically lowered Lp(a) level was associated with a 29% lower risk of CHD (odds ratio [OR]: 0.71; 95% confidence interval [CI]: 0.69 to 0.73), a 31% lower risk of peripheral vascular disease (OR: 0.69; 95% CI: 0.59 to 0.80), a 13% lower risk of stroke (OR: 0.87; 95% CI: 0.79 to 0.96), a 17% lower risk of heart failure (OR: 0.83; 95% CI: 0.73 to 0.94), and a 37% lower risk of aortic stenosis (OR: 0.63; 95% CI: 0.47 to 0.83). We observed no association with 31 other disorders, including type 2 diabetes and cancer. Variants that led to gain of LPA gene function increased the risk for CHD, whereas those that led to loss of gene function reduced the CHD risk.

conclusionsBeyond CHD, genetically lowered Lp(a) levels are associated with a lower risk of peripheral vascular disease, stroke, heart failure, and aortic stenosis. As such, pharmacological lowering of plasma Lp(a) may influence a range of atherosclerosis-related diseases.

Indexed as

BiomarkersCoronary DiseaseDNAFemaleGenetic TherapyGenome-Wide Association StudyHumansLipoprotein(a)MalePhenotypePolymorphism, Single NucleotidePrognosisRisk FactorsBiomarkersDNALipoprotein(a)coronary heart diseasegeneticsphenome-wide association studysingle nucleotide polymorphism

Identifiers

PMID28007139
PMCPMC5328146
OpenAlexW2564082722

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.