Evidence map›Paper›PMID 30413934›Full record

ArticleActa neuropathologica2019

Dissecting the genetic relationship between cardiovascular risk factors and Alzheimer's disease.

Iris J Broce, Chin Hong Tan, Chun Chieh Fan, Iris Jansen, Jeanne E Savage, Aree Witoelar, Natalie Wen, Christopher P Hess, William P Dillon, Christine M Glastonbury and 24 more

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

Article in Acta neuropathologica, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
80citing papers in PubMed, 3 pooled it
12.1field-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

80 citing papers in PubMed, 3 syntheses or guidelines pooled it, 141 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Article
  5. Stratification by a polygenic risk score of common variation aids in Alzheimer's disease rare variant discovery.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Observational
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  7. Review
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  17. GlialProceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  18. Article
  19. Choriocapillaris reduction accurately discriminates against early-onset Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024
    Article
  20. Article

20 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

34 authors at 15 institutions in 4 countries.

Iris J BroceNeuroradiology Section, L-352, Department of Radiology and Biomedical Imaging, University of California, San Francisco, 505 Parnassus Avenue, San Francisco, CA, 94143, USA. iris.broce@ucsf.edu.
Chin Hong TanNeuroradiology Section, L-352, Department of Radiology and Biomedical Imaging, University of California, San Francisco, 505 Parnassus Avenue, San Francisco, CA, 94143, USA.
Chun Chieh FanDepartment of Cognitive Sciences, University of California, San Diego, La Jolla, CA, USA.
Iris JansenDepartment of Clinical Genetics, Vrije Universiteit Medical Center, Amsterdam, The Netherlands.
Jeanne E SavageDepartment of Clinical Genetics, Vrije Universiteit Medical Center, Amsterdam, The Netherlands.
Aree WitoelarNorwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Natalie WenDepartment of Psychiatry, Washington University in St Louis, 425 S Euclid Ave, Campus Box 8134, St Louis, MO, 63110, USA.
Christopher P HessNeuroradiology Section, L-352, Department of Radiology and Biomedical Imaging, University of California, San Francisco, 505 Parnassus Avenue, San Francisco, CA, 94143, USA.
William P DillonNeuroradiology Section, L-352, Department of Radiology and Biomedical Imaging, University of California, San Francisco, 505 Parnassus Avenue, San Francisco, CA, 94143, USA.
Christine M GlastonburyNeuroradiology Section, L-352, Department of Radiology and Biomedical Imaging, University of California, San Francisco, 505 Parnassus Avenue, San Francisco, CA, 94143, USA.
Maria GlymourDepartment of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA.
Jennifer S YokoyamaDepartment of Neurology, University of California, San Francisco, CA, USA.
Fanny M ElahiDepartment of Neurology, University of California, San Francisco, CA, USA.
Gil D RabinoviciDepartment of Neurology, University of California, San Francisco, CA, USA.
Bruce L MillerDepartment of Neurology, University of California, San Francisco, CA, USA.
Elizabeth C MorminoDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, CA, USA.
Reisa A SperlingDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
David A BennettRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
Linda K McEvoyDepartment of Radiology, University of California, San Diego, La Jolla, CA, USA.
James B BrewerDepartment of Radiology, University of California, San Diego, La Jolla, CA, USA.
Howard H FeldmanDepartment of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
Bradley T HymanDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Margaret Pericak-VanceJohn P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, USA.
Jonathan L HainesDepartment of Epidemiology and Biostatistics, Case Western University, Cleveland, OH, USA.
Lindsay A FarrerDepartment of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA, USA.
Richard MayeuxDepartment of Neurology, Columbia University, New York, NY, USA.
Gerard D SchellenbergDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Kristine YaffeDepartment of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA.
Leo P SugrueNeuroradiology Section, L-352, Department of Radiology and Biomedical Imaging, University of California, San Francisco, 505 Parnassus Avenue, San Francisco, CA, 94143, USA.
Anders M DaleDepartment of Cognitive Sciences, University of California, San Diego, La Jolla, CA, USA.
Danielle PosthumaDepartment of Clinical Genetics, Vrije Universiteit Medical Center, Amsterdam, The Netherlands.
Ole A AndreassenNorwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Celeste M KarchDepartment of Psychiatry, Washington University in St Louis, 425 S Euclid Ave, Campus Box 8134, St Louis, MO, 63110, USA. karchc@wustl.edu.
Rahul S DesikanNeuroradiology Section, L-352, Department of Radiology and Biomedical Imaging, University of California, San Francisco, 505 Parnassus Avenue, San Francisco, CA, 94143, USA. rahul.desikan@ucsf.edu.ORCID 0000-0002-4151-6017
University of California, San Francisco · USUniversity of California San Diego · USVrije Universiteit Amsterdam · NLUniversity of Oslo · NOWashington University in St. Louis · USBoston University · USBrigham and Women's Hospital · USCase Western Reserve University · USColumbia University · USHarvard University · USNanyang Technological University · SGRush University Medical Center · USStanford University · USUniversity of Miami · USUniversity of Pennsylvania · US

Funding

National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD)U24AG021886 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI TATIANA M. FOROUD · 2002 to 2026
$119.8M
Alzheimer's Disease Genetics ConsortiumU01AG032984 · NIA · UNIVERSITY OF PENNSYLVANIA · PI SCHELLENBERG, GERARD DAVID · 2009 to 2024
$60.4M
SUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1991 to 2020
$49.1M
EPIDEMIOLOGY OF NEURAL RESERVE AND NEUROBIOLOGY IN AGINGR01AG017917 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2001 to 2023
$43.3M
The National Institute on Aging (NIA) Late Onset of Alzheimer's Disease (LOAD) Family-Based Study (FBS)U24AG056270 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Gary Wayne Beecham, TATIANA M. FOROUD · 2017 to 2026
$31.4M
RISK FACTORS, PATHOLOGY, AND CLINICAL EXPRESSIONS OF ADR01AG015819 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1998 to 2024
$21.4M
Genetic Epidemiology of Cerebrovascular Factors in Alzheimer's DiseaseRF1AG054023 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI MAYEUX, RICHARD P · 2016 to 2018
$8.9M
Genetic Studies of Alzheimer's Disease in Caribbean HispanicsRF1AG015473 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI MAYEUX, RICHARD P · 2015 to 2018
$3.3M
Mentoring Imaging Research in Early ADK24AG035007 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI SPERLING, REISA A. · 2010 to 2020
$1.4M
RNA signatures of frontotemporal dementia and ALS due to C9ORF72 expansionK01AG049152 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI YOKOYAMA, JENNIFER S · 2015 to 2019
$648k
GENETIC DISRUPTION OF TAU METABOLISM IN TAUOPATHIESK01AG046374 · NIA · WASHINGTON UNIVERSITY · PI KARCH, CELESTE MARIE · 2014 to 2018
$568k
Medical Research Council MC_PC_17228Medical Research Council MC_QA137853NIA NIH HHS K01 AG046374NIA NIH HHS K01 AG049152NIA NIH HHS K24 AG035007NIA NIH HHS P30 AG010161NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017917NIA NIH HHS RF1 AG015473NIA NIH HHS RF1 AG054023NIA NIH HHS U01 AG032984NIA NIH HHS U24 AG021886NIA NIH HHS U24 AG056270Norges Forskningsråd 213837Norges Forskningsråd 223273Norges Forskningsråd 225989Norges Forskningsråd 237250/EU JPND
6 · The paper itself

Abstract

Cardiovascular (CV)- and lifestyle-associated risk factors (RFs) are increasingly recognized as important for Alzheimer's disease (AD) pathogenesis. Beyond the ε4 allele of apolipoprotein E (APOE), comparatively little is known about whether CV-associated genes also increase risk for AD. Using large genome-wide association studies and validated tools to quantify genetic overlap, we systematically identified single nucleotide polymorphisms (SNPs) jointly associated with AD and one or more CV-associated RFs, namely body mass index (BMI), type 2 diabetes (T2D), coronary artery disease (CAD), waist hip ratio (WHR), total cholesterol (TC), triglycerides (TG), low-density (LDL) and high-density lipoprotein (HDL). In fold enrichment plots, we observed robust genetic enrichment in AD as a function of plasma lipids (TG, TC, LDL, and HDL); we found minimal AD genetic enrichment conditional on BMI, T2D, CAD, and WHR. Beyond APOE, at conjunction FDR < 0.05 we identified 90 SNPs on 19 different chromosomes that were jointly associated with AD and CV-associated outcomes. In meta-analyses across three independent cohorts, we found four novel loci within MBLAC1 (chromosome 7, meta-p = 1.44 × 10

Indexed as

AgedAged, 80 and overAllelesAlzheimer DiseaseApolipoproteins ECardiovascular DiseasesCohort StudiesDiabetes Mellitus, Type 2FemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMaleMiddle AgedRisk FactorsApolipoproteins EAlzheimer’s diseaseCardiovascularGenetic pleiotropyLipidsPolygenic enrichment

Identifiers

PMID30413934
PMCPMC6358498
OpenAlexW2899829198

What OpenQuestion 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 OpenQuestion graph.