Evidence mapPaperPMID 34140684Full record

ArticleNature genetics2021

A unified framework identifies new links between plasma lipids and diseases from electronic medical records across large-scale cohorts.

Yogasudha Veturi, Anastasia Lucas, Yuki Bradford, Daniel Hui, Scott Dudek, Elizabeth Theusch, Anurag Verma, Jason E Miller, Iftikhar Kullo, Hakon Hakonarson and 13 more

Abstract read
In one paragraph

Article in Nature genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
field-weighted citation impact
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

9 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
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  8. Review
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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

23 authors.

Yogasudha VeturiDepartment of Genetics and Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Anastasia LucasDepartment of Genetics and Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Yuki BradfordDepartment of Genetics and Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Daniel HuiDepartment of Genetics and Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Scott DudekDepartment of Genetics and Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-2904-3824
Elizabeth TheuschDepartment of Pediatrics, University of California, San Francisco, Oakland, CA, USA.ORCID http://orcid.org/0000-0002-5678-759X
Anurag VermaDepartment of Genetics and Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Jason E MillerDepartment of Genetics and Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Iftikhar KulloDivision of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA.ORCID http://orcid.org/0000-0002-6524-3471
Hakon HakonarsonCenter for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-2814-7461
Patrick SleimanCenter for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Daniel SchaidDepartment of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
Charles M SteinDivision of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Digna R Velez EdwardsDepartment of Biomedical Informatics in School of Medicine, Vanderbilt University, Nashville, TN, USA.
QiPing FengDivision of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Wei-Qi WeiDepartment of Biomedical Informatics in School of Medicine, Vanderbilt University, Nashville, TN, USA.
Marisa W MedinaDepartment of Pediatrics, University of California, San Francisco, Oakland, CA, USA.ORCID http://orcid.org/0000-0002-3631-0129
Ronald M KraussDepartment of Pediatrics, University of California, San Francisco, Oakland, CA, USA.
Thomas J HoffmannInstitute for Human Genetics, and Department of Epidemiology & Biostatistics, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-6893-4449
Neil RischInstitute for Human Genetics, and Department of Epidemiology & Biostatistics, University of California, San Francisco, San Francisco, CA, USA.
Benjamin F VoightSystems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Daniel J RaderDepartment of Genetics and Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Marylyn D RitchieDepartment of Genetics and Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. marylyn@pennmedicine.upenn.edu.ORCID http://orcid.org/0000-0002-1208-1720

Funding

Genomic Basis of Susceptibility to COVID-19 Infection and its ComplicationsU01HG006379 · NHGRI · MAYO CLINIC ROCHESTER · PI Richard R. Sharp · 2011 to 2026
$16.5M
Pharmacogenomics of Statin TherapyP50GM115318 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI RISCH, NEIL J. · 2015 to 2019
$14.0M
Finding Genomic Profiles of COVID-19 Phenotypes from the EHRU01HG008685 · NHGRI · BRIGHAM AND WOMEN'S HOSPITAL · PI ELIZABETH W KARLSON, Matthew S Lebo · 2015 to 2026
$13.6M
Variation, Function, and Disease Supplement ProgramU01HG008657 · NHGRI · UNIVERSITY OF WASHINGTON · PI David Russell Crosslin, Gail Pairitz Jarvik · 2015 to 2026
$13.4M
OMOP information model for eMERGE phenotypingU01HG008680 · NHGRI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Wendy K Chung, GEORGE M HRIPCSAK · 2015 to 2026
$13.3M
Pharmacogenomics of HIV TherapyR01AI077505 · NIAID · VANDERBILT UNIVERSITY MEDICAL CENTER · PI HAAS, DAVID W · 2008 to 2025
$12.3M
DNA Sequencing Support for the eMERGE NetworkU01HG008664 · NHGRI · BAYLOR COLLEGE OF MEDICINE · PI GIBBS, RICHARD A · 2015 to 2019
$10.9M
Global Alliance for Genomic Health (GA4GH)U01HG008676 · NHGRI · BRIGHAM AND WOMEN'S HOSPITAL · PI LENNON, NIALL JOHN, REHM, HEIDI L · 2015 to 2019
$8.6M
The Electronic Medical Records and Genomics (eMERGE) Network Phase III Coordinating Center (U01)U01HG008701 · NHGRI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI PETERSON, JOSEPH F. · 2015 to 2019
$7.1M
VGER, the Vanderbilt Genome-Electronic Records ProjectU01HG008672 · NHGRI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI DENNY, JOSHUA C., RODEN, DAN M · 2015 to 2019
$5.1M
The Future of Genomics Medicine in Patient Care: Contributions from CHOPU01HG008684 · NHGRI · CHILDREN'S HOSP OF PHILADELPHIA · PI HAKONARSON, HAKON · 2015 to 2019
$5.0M
Systems Genetics Dissection of Non-alcoholic SteatohepatitisR01DK117850 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Aldons Jake Lusis · 2019 to 2026
$4.6M
Medical Research Council MC_PC_17228Medical Research Council MC_QA137853NHGRI NIH HHS R01 HG010067NHGRI NIH HHS T32 HG009495NHGRI NIH HHS U01 HG006379NHGRI NIH HHS U01 HG008657NHGRI NIH HHS U01 HG008664NHGRI NIH HHS U01 HG008666NHGRI NIH HHS U01 HG008672NHGRI NIH HHS U01 HG008673NHGRI NIH HHS U01 HG008676NHGRI NIH HHS U01 HG008679NHGRI NIH HHS U01 HG008680NHGRI NIH HHS U01 HG008684NHGRI NIH HHS U01 HG008685NHGRI NIH HHS U01 HG008701NIAID NIH HHS R01 AI077505NIDDK NIH HHS R01 DK101478NIDDK NIH HHS R01 DK117850NIDDK NIH HHS R56 DK101478NIGMS NIH HHS P50 GM115318NIGMS NIH HHS R35 GM131770
6 · The paper itself

Abstract

Plasma lipids are known heritable risk factors for cardiovascular disease, but increasing evidence also supports shared genetics with diseases of other organ systems. We devised a comprehensive three-phase framework to identify new lipid-associated genes and study the relationships among lipids, genotypes, gene expression and hundreds of complex human diseases from the Electronic Medical Records and Genomics (347 traits) and the UK Biobank (549 traits). Aside from 67 new lipid-associated genes with strong replication, we found evidence for pleiotropic SNPs/genes between lipids and diseases across the phenome. These include discordant pleiotropy in the HLA region between lipids and multiple sclerosis and putative causal paths between triglycerides and gout, among several others. Our findings give insights into the genetic basis of the relationship between plasma lipids and diseases on a phenome-wide scale and can provide context for future prevention and treatment strategies.

Indexed as

BiomarkersDisease SusceptibilityElectronic Health RecordsAllelesBiological Specimen BanksGenetic Association StudiesGenetic Predisposition to DiseaseHumansLipidsPolymorphism, Single NucleotidePublic Health SurveillanceQuantitative Trait, HeritableUnited KingdomBiomarkersLipids

Identifiers

PMID34140684
PMCPMC8555954

What Socratic holds

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Registered trials

None linked

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 Socratic graph.