Evidence map›Paper›PMID 30140000›Full record

ArticleNature communications2018

Deep-coverage whole genome sequences and blood lipids among 16,324 individuals.

Pradeep Natarajan, Gina M Peloso, Seyedeh Maryam Zekavat, May Montasser, Andrea Ganna, Mark Chaffin, Amit V Khera, Wei Zhou, Jonathan M Bloom, Jesse M Engreitz and 27 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
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. Cited by 101 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
101citing papers in PubMed, 7 pooled it
21.2field-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

101 citing papers in PubMed, 7 syntheses or guidelines pooled it, 199 citations in OpenAlex.

  1. Pooled it
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  8. Identifying the Lipidomic Effects of a Rare Loss-of-Function Deletion inCirculation. Genomic and precision medicine · 2021
    Trial
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  14. A sex-specific genome-wide association study of blood lipid levels in All of Us.medRxiv : the preprint server for health sciences · 2025
    Article
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41 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

37 authors at 20 institutions in 5 countries.

Pradeep NatarajanCenter for Genomic Medicine and Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, 02114, USA.ORCID http://orcid.org/0000-0001-8402-7435
Gina M PelosoDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, 02118, USA.
Seyedeh Maryam ZekavatBroad Institute of Harvard & MIT, Cambridge, MA, 02142, USA.ORCID http://orcid.org/0000-0003-4026-8944
May MontasserSchool of Medicine, University of Maryland, Baltimore, MD, 21201, USA.
Andrea GannaBroad Institute of Harvard & MIT, Cambridge, MA, 02142, USA.
Mark ChaffinBroad Institute of Harvard & MIT, Cambridge, MA, 02142, USA.ORCID http://orcid.org/0000-0002-1234-5562
Amit V KheraCenter for Genomic Medicine and Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, 02114, USA.
Wei ZhouDepartment of Computational Medicine and Bioinformatics, School of Public Health, University of Michigan, Ann Arbor, MI, 48109, USA.
Jonathan M BloomBroad Institute of Harvard & MIT, Cambridge, MA, 02142, USA.ORCID http://orcid.org/0000-0001-8497-1434
Jesse M EngreitzBroad Institute of Harvard & MIT, Cambridge, MA, 02142, USA.ORCID http://orcid.org/0000-0002-5754-1719
Jason ErnstDepartment of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA, 90095, USA.ORCID http://orcid.org/0000-0003-4026-7853
Jeffrey R O'ConnellSchool of Medicine, University of Maryland, Baltimore, MD, 21201, USA.
Sanni E RuotsalainenInstitute for Molecular Medicine Finland, Helsinki, 00290, Finland.
Maris AlverEstonian Genome Center, University of Tartu, Tartu, 51010, Estonia.
Ani ManichaikulCenter for Public Health Genomics, University of Virginia, Charlottesville, VA, 22908, USA.
W Craig JohnsonDepartment of Biostatistics, University of Washington, Seattle, WA, 98195, USA.
James A PerrySchool of Medicine, University of Maryland, Baltimore, MD, 21201, USA.ORCID http://orcid.org/0000-0001-5050-2074
Timothy PoterbaBroad Institute of Harvard & MIT, Cambridge, MA, 02142, USA.
Cotton SeedBroad Institute of Harvard & MIT, Cambridge, MA, 02142, USA.
Ida L SurakkaInstitute for Molecular Medicine Finland, Helsinki, 00290, Finland.
Tonu EskoEstonian Genome Center, University of Tartu, Tartu, 51010, Estonia.ORCID http://orcid.org/0000-0003-1982-6569
Samuli RipattiInstitute for Molecular Medicine Finland, Helsinki, 00290, Finland.
Veikko SalomaaInstitute for Molecular Medicine Finland, Helsinki, 00290, Finland.ORCID http://orcid.org/0000-0001-7563-5324
Adolfo CorreaDepartment of Medicine, University of Mississippi Medical Center, Jackson, MS, 39216, USA.ORCID http://orcid.org/0000-0002-9501-600X
Ramachandran S VasanSections of Preventive Medicine and Epidemiology and Cardiology, Department of Medicine, Boston University School of Medicine, Boston, MA, 02118, USA.
Manolis KellisBroad Institute of Harvard & MIT, Cambridge, MA, 02142, USA.
Benjamin M NealeCenter for Genomic Medicine and Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, 02114, USA.ORCID http://orcid.org/0000-0003-1513-6077
Eric S LanderBroad Institute of Harvard & MIT, Cambridge, MA, 02142, USA.
Goncalo AbecasisDepartment of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI, 48109, USA.
Braxton MitchellSchool of Medicine, University of Maryland, Baltimore, MD, 21201, USA.
Stephen S RichCenter for Public Health Genomics, University of Virginia, Charlottesville, VA, 22908, USA.
James G WilsonDepartment of Medicine, University of Mississippi Medical Center, Jackson, MS, 39216, USA.
L Adrienne CupplesDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, 02118, USA.
Jerome I RotterInstitute for Translational Genomics and Population Sciences, LABioMed and Departments of Pediatrics and Medicine, Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.
Cristen J WillerDepartments of Human Genetics, Internal Medicine, and Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, 48109, USA.ORCID http://orcid.org/0000-0001-5645-4966
Sekar KathiresanCenter for Genomic Medicine and Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, 02114, USA. skathiresan1@mgh.harvard.edu.ORCID http://orcid.org/0000-0002-6724-032X
NHLBI TOPMed Lipids Working Group
University of Washington · USUniversity of Maryland, Baltimore · USUniversity of Michigan · USBrigham and Women's Hospital · USJohns Hopkins University · USUniversity of Colorado Denver · USBroad Institute · USNational Institutes of Health · USUniversity of Mississippi · USIcahn School of Medicine at Mount Sinai · USNational Jewish Health · USNew York Genome Center · USThe University of Texas Rio Grande Valley · USUniversity of Virginia · USWashington University in St. Louis · USBoston University · USMassachusetts General Hospital · USStanford University · USThe Lundquist Institute · USUniversity of Alabama at Birmingham · US

Funding

Large Scale Sequencing and Analysis of GenomesU54HG003067 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GABRIEL, STACEY, LANDER, ERIC S · 2004 to 2015
$568.6M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007205 · NIGMS · YALE UNIVERSITY · PI KAZMIERCZAK, BARBARA I · 1985 to 2019
$42.9M
Tracking and Evaluation CoreU54GM115428 · NIGMS · UNIVERSITY OF MISSISSIPPI MED CTR · PI COMPRETTA, CAROLINE E. · 2016 to 2025
$38.2M
Cell Interactions in the Inflamed Intestinal MucosaR01DK075787 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI JOEL N HIRSCHHORN · 2007 to 2026
$13.1M
Studies of Rare Genetic Variation in the Isolated Population of SardiniaR01HL117626 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ABECASIS, GONCALO · 2013 to 2016
$10.5M
Rare variants and NHLBI traits in deeply phenotyped cohortsR01HL120393 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M, RICE, KENNETH M. · 2014 to 2016
$8.9M
Using genetics to discover mechanisms of myocardial infarctionR01HL109946 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI YUQING Eugene CHEN, Ida Liisa Surakka · 2011 to 2026
$8.9M
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
A Family-based Exome Sequencing Approach to Identify Platelet Aggregation GenesR01HL112064 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI MATHIAS, RASIKA ANN · 2012 to 2015
$5.1M
Whole 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
$4.7M
Natural Genetic Variation in the Human GenomeR01HG002898 · NHGRI · UNIVERSITY OF MARYLAND BALTIMORE · PI DEVINE, SCOTT E · 2004 to 2019
$3.7M
American Heart Association (American Heart Association, Inc.) 17SDG33680041NCATS NIH HHS KL2 TR001100NHGRI NIH HHS R01 HG002898NHGRI NIH HHS U54 HG003067NHLBI NIH HHS F30 HL107066NHLBI NIH HHS HHSN268201100037CNHLBI NIH HHS HHSN268201500014CNHLBI NIH HHS K01 HL125751NHLBI NIH HHS K01 HL130609NHLBI NIH HHS K01 HL136700NHLBI NIH HHS K08 HL140203NHLBI NIH HHS R01 HL109946NHLBI NIH HHS R01 HL112064NHLBI NIH HHS R01 HL117626NHLBI NIH HHS R01 HL120393NHLBI NIH HHS R01 HL121007NHLBI NIH HHS R01 HL127564NHLBI NIH HHS R01 HL138737NHLBI NIH HHS R01 HL142711NHLBI NIH HHS R03 HL141439NHLBI NIH HHS T32 HL139439NHLBI NIH HHS U01 HL137162NIA NIH HHS K01 AG059898NIDDK NIH HHS R01 DK075787NIGMS NIH HHS T32 GM007205NIGMS NIH HHS U54 GM115428
6 · The paper itself

Abstract

Large-scale deep-coverage whole-genome sequencing (WGS) is now feasible and offers potential advantages for locus discovery. We perform WGS in 16,324 participants from four ancestries at mean depth >29X and analyze genotypes with four quantitative traits-plasma total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, and triglycerides. Common variant association yields known loci except for few variants previously poorly imputed. Rare coding variant association yields known Mendelian dyslipidemia genes but rare non-coding variant association detects no signals. A high 2M-SNP LDL-C polygenic score (top 5th percentile) confers similar effect size to a monogenic mutation (~30 mg/dl higher for each); however, among those with severe hypercholesterolemia, 23% have a high polygenic score and only 2% carry a monogenic mutation. At these sample sizes and for these phenotypes, the incremental value of WGS for discovery is limited but WGS permits simultaneous assessment of monogenic and polygenic models to severe hypercholesterolemia.

Indexed as

Genome, HumanBase SequenceCholesterol, LDLGene FrequencyGenome-Wide Association StudyHigh-Throughput Nucleotide SequencingHumansLipidsModels, GeneticMutationCholesterol, LDLLipids

Identifiers

PMID30140000
PMCPMC6107638
OpenAlexW2771599286

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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.