Evidence map›Paper›PMID 37051669›Full record

SynthesisAlzheimer's & dementia : the journal of the Alzheimer's Association2023

A haptoglobin (HP) structural variant alters the effect of APOE alleles on Alzheimer's disease.

Haimeng Bai, Adam C Naj, Penelope Benchek, Logan Dumitrescu, Timothy Hohman, Kara Hamilton-Nelson, Asha R Kallianpur, Anthony J Griswold, Badri Vardarajan, Eden R Martin and 9 more

Open access · hybridAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.7field-weighted citation impact, top 18% 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

10 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
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  3. Article
  4. Article
  5. Article
  6. Long-read genome sequencing and multi-omics in aging and neurodegeneration.medRxiv : the preprint server for health sciences · 2025
    Article
  7. Article
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  9. 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

19 authors at 9 institutions in 1 country.

Haimeng BaiCleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, Ohio, USA.
Adam C NajDepartment of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Penelope BenchekCleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, Ohio, USA.
Logan DumitrescuVanderbilt Memory & Alzheimer's Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Timothy HohmanVanderbilt Memory & Alzheimer's Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Kara Hamilton-NelsonJohn P. Hussman Institute for Human Genomics, University of Miami, Miami, Florida, USA.
Asha R KallianpurGenomic Medicine Institute, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
Anthony J GriswoldJohn P. Hussman Institute for Human Genomics, University of Miami, Miami, Florida, USA.
Badri VardarajanDepartment of Neurology, The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, USA.
Eden R MartinJohn P. Hussman Institute for Human Genomics, University of Miami, Miami, Florida, USA.
Gary W BeechamJohn P. Hussman Institute for Human Genomics, University of Miami, Miami, Florida, USA.
Jennifer E BelowVanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Gerard SchellenbergPenn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Richard MayeuxDepartment of Neurology, The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, USA.
Lindsay FarrerDepartments of Medicine (Biomedical Genetics), Neurology, Ophthalmology, Biostatistics, and Epidemiology, Boston University Schools of Medicine and Public Health, Boston, Massachusetts, USA.
Margaret A Pericak-VanceJohn P. Hussman Institute for Human Genomics, University of Miami, Miami, Florida, USA.
Jonathan L HainesCleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, Ohio, USA.
William S BushCleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, Ohio, USA.
Alzheimer's Disease Genetics Consortium
Dr. John T. Macdonald Foundation · USVanderbilt University Medical Center · USCase Western Reserve University · USColumbia University · USUniversity of Miami · USUniversity of Pennsylvania · USUniversity School · USBoston Public Schools · USCleveland Clinic Lerner College of Medicine · 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
NATIONAL ALZHEIMERS COORDINATING CENTER (NACC)U01AG016976 · NIA · UNIVERSITY OF WASHINGTON · PI KUKULL, WALTER ANTHONY · 1999 to 2020
$72.8M
Alzheimer's Disease Genetics ConsortiumU01AG032984 · NIA · UNIVERSITY OF PENNSYLVANIA · PI SCHELLENBERG, GERARD DAVID · 2009 to 2024
$60.4M
THERAPEUTIC EFFECTS OF INTRA-NASAL INSULIN DETEMIRP50AG005136 · NIA · UNIVERSITY OF WASHINGTON · PI GRABOWSKI, THOMAS J. · 1985 to 2019
$57.2M
VIRUS-INDUCED BRAIN PATHOLOGYP50AG005131 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BREWER, JAMES B · 1985 to 2018
$55.4M
WASHINGTON UNIVERSITY ALZHEIMERS DISEASE RESEARCH CENTERP50AG005681 · NIA · WASHINGTON UNIVERSITY · PI FAGAN, ANNE · 1985 to 2019
$52.1M
SUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI LEURGANS, SUE E. · 1991 to 2020
$49.1M
Satellite Diagnostic and Treatment Clinic CoreP50AG008702 · NIA · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI DE JAGER, PHILIP L · 1989 to 2019
$46.3M
TREATMENT OF DEPRESSION IN ALZHEIMER'S DISEASEP50AG005133 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KAMBOH, M. ILYAS · 1985 to 2019
$43.0M
THE NIA GENETICS OF ALZHEIMER'S DISEASE DATA STORAGE SITEU24AG041689 · NIA · UNIVERSITY OF PENNSYLVANIA · PI LI-SAN WANG · 2012 to 2026
$42.3M
THE ROLE OF ADVANCED CAA IN ALZHEIMER'S DEMENTIAP50AG005134 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI HYMAN, BRADLEY T. · 1985 to 2018
$42.1M
VASCULAR RISK AND COGNITIVE STATUS IN A LATINO POPULATIONP50AG005142 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI BRASKIE, MEREDITH NICOLE · 1985 to 2019
$41.0M
NHLBI NIH HHS R01 HL117626NHLBI NIH HHS R01 HL120393NIA NIH HHS P30 AG008017NIA NIH HHS P30 AG008051NIA NIH HHS P30 AG010124NIA NIH HHS P30 AG010129NIA NIH HHS P30 AG010133NIA NIH HHS P30 AG010161NIA NIH HHS P30 AG012300NIA NIH HHS P30 AG013846NIA NIH HHS P30 AG013854NIA NIH HHS P30 AG019610NIA NIH HHS P30 AG028383NIA NIH HHS P30 AG035982NIA NIH HHS P50 AG005131NIA NIH HHS P50 AG005133NIA NIH HHS P50 AG005134NIA NIH HHS P50 AG005136NIA NIH HHS P50 AG005138NIA NIH HHS P50 AG005142NIA NIH HHS P50 AG005146NIA NIH HHS P50 AG005681NIA NIH HHS P50 AG008702NIA NIH HHS P50 AG016570NIA NIH HHS P50 AG016573NIA NIH HHS P50 AG016574NIA NIH HHS P50 AG023501NIA NIH HHS P50 AG025688NIA NIH HHS P50 AG033514NIA NIH HHS R01 AG059716NIA NIH HHS RF1 AG059018NIA NIH HHS RF1 AG061351NIA NIH HHS U01 AG016976NIA NIH HHS U01 AG032984NIA NIH HHS U24 AG041689
6 · The paper itself

Abstract

backgroundHaptoglobin (HP) is an antioxidant of apolipoprotein E (APOE), and previous reports have shown HP binds with APOE and amyloid beta (Aβ) to aid its clearance. A common structural variant of the HP gene distinguishes it into two alleles: HP1 and HP2.

methodsHP genotypes were imputed in 29 cohorts from the Alzheimer's Disease Genetics Consortium (N = 20,512). Associations between the HP polymorphism and Alzheimer's disease (AD) risk and age of onset through APOE interactions were investigated using regression models.

resultsThe HP polymorphism significantly impacts AD risk in European-descent individuals (and in meta-analysis with African-descent individuals) by modifying both the protective effect of APOE ε2 and the detrimental effect of APOE ε4. The effect is particularly significant among APOE ε4 carriers. DISCUSSION: The effect modification of APOE by HP suggests adjustment and/or stratification by HP genotype is warranted when APOE risk is considered. Our findings also provided directions for further investigations on potential mechanisms behind this association.

Indexed as

Alzheimer DiseaseAllelesAmyloid beta-PeptidesApolipoprotein E4Apolipoproteins EGenotypeHaptoglobinsHumansAmyloid beta-PeptidesApolipoprotein E4Apolipoproteins EHaptoglobinsage at onsetAlzheimer's diseaseapolipoprotein Ehaptoglobin polymorphism

Identifiers

PMID37051669
PMCPMC13047925
OpenAlexW4365442795

What Socratic holds

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LicenceCC BY-NC
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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.