Evidence map›Paper›PMID 34459398›Full record

ArticleJournal of Alzheimer's disease : JAD2021

Assessing Genetic Overlap and Causality Between Blood Plasma Proteins and Alzheimer's Disease.

Alex Handy, Jodie Lord, Rebecca Green, Jin Xu, Dag Aarsland, Latha Velayudhan, Abdul Hye, Richard Dobson, Petroula Proitsi, Alzheimer’s Disease Neuroimaging initiative and 1 more

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

Article in Journal of Alzheimer's disease : JAD, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.1field-weighted citation impact, top 24% 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

6 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
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  5. BCG Vaccine-The Road Not Taken.Microorganisms · 2022
    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

11 authors at 2 institutions in 2 countries.

Alex HandyUniversity College London, Institute of Health Informatics, London, UK.
Jodie LordKing's College London, Institute of Psychiatry, Psychology and Neuroscience, London, UK.
Rebecca GreenKing's College London, Institute of Psychiatry, Psychology and Neuroscience, London, UK.
Jin XuKing's College London, Institute of Psychiatry, Psychology and Neuroscience, London, UK.
Dag AarslandKing's College London, Institute of Psychiatry, Psychology and Neuroscience, London, UK.
Latha VelayudhanKing's College London, Institute of Psychiatry, Psychology and Neuroscience, London, UK.
Abdul HyeKing's College London, Institute of Psychiatry, Psychology and Neuroscience, London, UK.
Richard DobsonUniversity College London, Institute of Health Informatics, London, UK.
Petroula ProitsiKing's College London, Institute of Psychiatry, Psychology and Neuroscience, London, UK.
Alzheimer’s Disease Neuroimaging initiative
AddNeuroMed, and the GERAD1 Consortium
King's College London · GBUniversity of London · GB

Funding

Alzheimer's Disease Neuroimaging InitiativeU01AG024904 · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · 2004 to 2005
$21.3M
British Heart FoundationChief Scientist OfficeCIHRDepartment of HealthMedical Research Council MC_PC_17214NIA NIH HHS U01 AG024904Wellcome Trust
6 · The paper itself

Abstract

backgroundBlood plasma proteins have been associated with Alzheimer's disease (AD), but understanding which proteins are on the causal pathway remains challenging.

objectiveInvestigate the genetic overlap between candidate proteins and AD using polygenic risk scores (PRS) and interrogate their causal relationship using bi-directional Mendelian randomization (MR).

methodsFollowing a literature review, 31 proteins were selected for PRS analysis. PRS were constructed for prioritized proteins with and without the apolipoprotein E region (APOE+/-PRS) and tested for association with AD status across three cohorts (n = 6,244). An AD PRS was also tested for association with protein levels in one cohort (n = 410). Proteins showing association with AD were taken forward for MR.

resultsFor APOE ɛ3, apolipoprotein B-100, and C-reactive protein (CRP), protein APOE+ PRS were associated with AD below Bonferroni significance (pBonf, p < 0.00017). No protein APOE- PRS or AD PRS (APOE+/-) passed pBonf. However, vitamin D-binding protein (protein PRS APOE-, p = 0.009) and insulin-like growth factor-binding protein 2 (AD APOE- PRS p = 0.025, protein APOE- PRS p = 0.045) displayed suggestive signals and were selected for MR. In bi-directional MR, none of the five proteins demonstrated a causal association (p < 0.05) in either direction.

conclusionApolipoproteins and CRP PRS are associated with AD and provide a genetic signal linked to a specific, accessible risk factor. While evidence of causality was limited, this study was conducted in a moderate sample size and provides a framework for larger samples with greater statistical power.

Indexed as

Alzheimer DiseaseMendelian Randomization AnalysisAgedApolipoproteins EBlood ProteinsFemaleGenome-Wide Association StudyHumansMaleMultifactorial InheritanceSomatomedinsApoE protein, humanApolipoproteins EBlood ProteinsSomatomedinsAlzheimer’s diseaseapolipoprotein B-100apolipoprotein Eblood proteinsC-reactive proteininsulin-like growth factor binding protein 2mendelian randomization analysispolygenic traitvitamin D-binding protein

Identifiers

PMID34459398
PMCPMC8609677
OpenAlexW3197768656

What Socratic holds

Textmetadata
LicenceCC BY-NC
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.