Evidence map›Paper›PMID 32277781›Full record

ArticleAnnals of neurology2020

Genetically Elevated LDL Associates with Lower Risk of Intracerebral Hemorrhage.

Guido J Falcone, Elayna Kirsch, Julian N Acosta, Rommell B Noche, Audrey Leasure, Sandro Marini, Jaeyoon Chung, Magdy Selim, James F Meschia, Devin L Brown and 29 more

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

Article in Annals of neurology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed, 4 pooled it
5.6field-weighted citation impact, top 4% 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

34 citing papers in PubMed, 4 syntheses or guidelines pooled it, 55 citations in OpenAlex.

  1. Mendelian randomization studies on cardiometabolic factors and intracranial aneurysms: A systematic literature analysis.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025
    Pooled it
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  6. Genetics of intracerebral hemorrhage.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026
    Review
  7. Leveraging Mendelian randomization to inform drug discovery and development for ischemic stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026
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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

39 authors at 18 institutions in 8 countries.

Guido J FalconeDivision of Neurocritical Care & Emergency Neurology, Department of Neurology, Yale School of Medicine, New Haven, CT, USA.ORCID 0000-0002-6407-0302
Elayna KirschDivision of Neurocritical Care & Emergency Neurology, Department of Neurology, Yale School of Medicine, New Haven, CT, USA.
Julian N AcostaDivision of Neurocritical Care & Emergency Neurology, Department of Neurology, Yale School of Medicine, New Haven, CT, USA.
Rommell B NocheDivision of Neurocritical Care & Emergency Neurology, Department of Neurology, Yale School of Medicine, New Haven, CT, USA.
Audrey LeasureDivision of Neurocritical Care & Emergency Neurology, Department of Neurology, Yale School of Medicine, New Haven, CT, USA.ORCID 0000-0002-9462-5022
Sandro MariniCenter for Genomic Medicine, Massachusetts General Hospital (MGH), Boston, MA, USA.
Jaeyoon ChungCenter for Genomic Medicine, Massachusetts General Hospital (MGH), Boston, MA, USA.
Magdy SelimDepartment of Neurology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA, USA.
James F MeschiaDepartment of Neurology, Mayo Clinic, Jacksonville, FL, USA.ORCID 0000-0002-4475-8142
Devin L BrownStroke Program, Department of Neurology, University of Michigan Health System, Ann Arbor, MI, USA.
Bradford B WorrallDepartment of Neurology and Public Health Sciences, University of Virginia Health System, Charlottesville, VA, USA.
David L TirschwellStroke Center, Harborview Medical Center, University of Washington, Seattle, WA, USA.
Jeremiasz M JagiellaDepartment of Neurology, Jagiellonian University Medical College, Kraków, Poland.
Helena SchmidtInstitute of Molecular Biology and Medical Biochemistry, Medical University Graz, Graz, Austria.
Jordi Jimenez-CondeNeurovascular Research Unit, Department of Neurology, Institut Municipal d'Investigacio' Medica-Hospital del Mar, Universitat Autonoma de Barcelona, Barcelona, Spain.
Israel Fernandez-CadenasNeurovascular Research Laboratory and Neurovascular Unit, Institut de Recerca, Hospital Vall d'Hebron, Universitat Autonoma de Barcelona, Barcelona, Spain.
Arne LindgrenDepartment of Clinical Sciences Lund, Neurology, Lund University, Lund, Sweden.
Agnieszka SlowikDepartment of Neurology, Jagiellonian University Medical College, Kraków, Poland.
Dipender GillDepartment of Epidemiology and Biostatistics and Department of Stroke Medicine, Imperial College London, London, UK.
Michael HolmesMedical Research Council Population Health Research Unit, University of Oxford, Oxford, UK.
Chia-Ling PhuahDepartment of Neurology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
Nils H PetersenDivision of Neurocritical Care & Emergency Neurology, Department of Neurology, Yale School of Medicine, New Haven, CT, USA.
Charles N Matouk MdDepartment of Neurosurgery, Yale School of Medicine, New Haven, CT, USA.
Murat GunelDepartment of Neurosurgery, Yale School of Medicine, New Haven, CT, USA.
Lauren SansingDivision of Vascular Neurology and Stroke, Department of Neurology, Yale School of Medicine, New Haven, CT, USA.
Derrick BennettClinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, Medical Research Council Population Health Research Unit, University of Oxford, Oxford, UK.
Zhengming ChenClinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, Medical Research Council Population Health Research Unit, University of Oxford, Oxford, UK.
Luan L SunCardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Robert ClarkeDivision of Neurocritical Care & Emergency Neurology, Department of Neurology, Yale School of Medicine, New Haven, CT, USA.
Robin G WaltersMedical Research Council Population Health Research Unit, University of Oxford, Oxford, UK.
Thomas M GillDepartment of Internal Medicine, Geriatric Medicine, Yale School of Medicine, New Haven, CT, USA.
Alessandro BiffiCenter for Genomic Medicine, Massachusetts General Hospital (MGH), Boston, MA, USA.ORCID 0000-0001-7063-455X
Sekar KathiresanCenter for Genomic Medicine, Massachusetts General Hospital (MGH), Boston, MA, USA.
Carl D LangefeldDepartment of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Daniel WooDepartment of Neurology, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Jonathan RosandCenter for Genomic Medicine, Massachusetts General Hospital (MGH), Boston, MA, USA.
Kevin N ShethDivision of Neurocritical Care & Emergency Neurology, Department of Neurology, Yale School of Medicine, New Haven, CT, USA.
Christopher D AndersonCenter for Genomic Medicine, Massachusetts General Hospital (MGH), Boston, MA, USA.
International Stroke Genetics Consortium
Yale University · USBroad Institute · USPopulation Council · INJagiellonian University · PLMassachusetts General Hospital · USUniversitat Autònoma de Barcelona · ESBeth Israel Deaconess Medical Center · USImperial College London · GBJacksonville College · USLund University · SEUniversity of Cambridge · GBUniversity of Cincinnati Medical Center · USUniversity of Graz · ATUniversity of Michigan · USUniversity of Virginia Health System · USUniversity of Washington · USWake Forest University · USWashington University in St. Louis · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Yale Study Support Suite (YES3): Dashboard and Web Portal Software Supporting Research Workflow through integrated, customizable REDCap External ModulesP30AG021342 · NIA · YALE UNIVERSITY · PI Lauren Ferrante · 2002 to 2026
$37.9M
Ethnic/Racial Variation in Intracerebral Hemorrhage (ERICH)U01NS069763 · NINDS · UNIVERSITY OF CINCINNATI · PI ANDERSON, CHRISTOPHER DAVID, DEMEL, STACIE · 2010 to 2024
$34.2M
StATins Use in intRacerebral hemorrhage patieNts (SATURN)U01NS102289 · NINDS · BETH ISRAEL DEACONESS MEDICAL CENTER · PI Magdy H Selim · 2019 to 2026
$15.7M
Genetic&Environment Risk Factors for Hemorrhagic StrokeR01NS036695 · NINDS · UNIVERSITY OF CINCINNATI · PI WOO, DANIEL · 1997 to 2012
$14.1M
Recurrent Hemorrhagic Stroke in Minority PopulationsR01NS093870 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI JONATHAN ROSAND, Amytis Towfighi · 2016 to 2026
$12.3M
Futility Study of Deferoxamine Mesylate in Intracerebral Hemorrhage (i-DEF)U01NS074425 · NINDS · BETH ISRAEL DEACONESS MEDICAL CENTER · PI SELIM, MAGDY H · 2012 to 2016
$8.7M
ICH Recovery GrantR01NS100417 · NINDS · UNIVERSITY OF CINCINNATI · PI WOO, DANIEL · 2017 to 2021
$5.3M
The Recovery in Stroke Using PAP (RISE UP) StudyR01NR018335 · NINR · YALE UNIVERSITY · PI REDEKER, NANCY S, SHETH, KEVIN NAVIN · 2019 to 2023
$3.4M
Sequencing Annotation and Functional Analysis in Risk of Intracerebral HemorrhageR01NS103924 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI ANDERSON, CHRISTOPHER DAVID · 2018 to 2022
$3.4M
Clinical Research Sites for the Network of Excellence in Neuroscience Clinical Trials (NeuroNEXT sites)U24NS107200 · NINDS · UNIVERSITY OF CINCINNATI · PI Brandon Foreman, TRACY A GLAUSER · 2018 to 2026
$3.3M
Southern New England Partnership In Stroke Research, Innovation and Treatment (SPIRIT)U24NS107215 · NINDS · YALE UNIVERSITY · PI MARK Jay ALBERTS, Karen L Furie · 2018 to 2026
$3.0M
American Heart Association-American Stroke Association 18POST34080063Medical Research Council MC_PC_13049Medical Research Council MC_PC_14135Medical Research Council MC_PC_17228Medical Research Council MC_QA137853Medical Research Council MC_U137686851Medical Research Council MC_UU_00017/1Medical Research Council MC_UU_12026/2NCATS NIH HHS UL1 TR001863NIA NIH HHS K07 AG043587NIA NIH HHS K76 AG059992NIA NIH HHS P30 AG021342NINDS NIH HHS K23 NS086873NINDS NIH HHS R01 NS036695NINDS NIH HHS R01 NS093870NINDS NIH HHS R01 NS100417NINDS NIH HHS R01 NS103924NINDS NIH HHS R03 NS112859NINDS NIH HHS R24 NS092983NINDS NIH HHS T32 NS100663NINDS NIH HHS U01 NS069763NINDS NIH HHS U01 NS074425NINDS NIH HHS U01 NS102289NINDS NIH HHS U24 NS107136NINDS NIH HHS U24 NS107200NINDS NIH HHS U24 NS107215NINR NIH HHS R01 NR018335Wellcome Trust 212946/Z/18/Z
6 · The paper itself

Abstract

objectiveObservational studies point to an inverse correlation between low-density lipoprotein (LDL) cholesterol levels and risk of intracerebral hemorrhage (ICH), but it remains unclear whether this association is causal. We tested the hypothesis that genetically elevated LDL is associated with reduced risk of ICH.

methodsWe constructed one polygenic risk score (PRS) per lipid trait (total cholesterol, LDL, high-density lipoprotein [HDL], and triglycerides) using independent genomewide significant single nucleotide polymorphisms (SNPs) for each trait. We used data from 316,428 individuals enrolled in the UK Biobank to estimate the effect of each PRS on its corresponding trait, and data from 1,286 ICH cases and 1,261 matched controls to estimate the effect of each PRS on ICH risk. We used these estimates to conduct Mendelian Randomization (MR) analyses.

resultsWe identified 410, 339, 393, and 317 lipid-related SNPs for total cholesterol, LDL, HDL, and triglycerides, respectively. All four PRSs were strongly associated with their corresponding trait (all p < 1.00 × 10

interpretationGenetically elevated LDL levels were associated with lower risk of ICH, providing support for a potential causal role of LDL cholesterol in ICH. ANN NEUROL 2020 ANN NEUROL 2020;88:56-66.

Indexed as

Genetic Predisposition to DiseaseAgedAged, 80 and overCerebral HemorrhageCholesterol, HDLCholesterol, LDLFemaleGenome-Wide Association StudyHumansMaleMiddle AgedPolymorphism, Single NucleotideTriglyceridesCholesterol, HDLCholesterol, LDLTriglycerides

Identifiers

PMID32277781
PMCPMC7523882
OpenAlexW3015648078

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

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.