Evidence map›Paper›PMID 35848024›Full record

ArticleJournal of Alzheimer's disease : JAD2022

Using Polygenic Hazard Scores to Predict Age at Onset of Alzheimer's Disease in Nordic Populations.

Ehsan Motazedi, Weiqiu Cheng, Jesper Q Thomassen, Oleksandr Frei, Arvid Rongve, Lavinia Athanasiu, Shahram Bahrami, Alexey Shadrin, Ingun Ulstein, Eystein Stordal and 20 more

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

Article in Journal of Alzheimer's disease : JAD, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
2.4field-weighted citation impact, top 12% 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

7 citing papers in PubMed, 13 citations in OpenAlex.

  1. Review
  2. Review
  3. Assessing polyomic risk to predict Alzheimer's disease using a machine learning model.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024
    Article
  4. Article
  5. TheProceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  6. Article
  7. Article
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

30 authors at 11 institutions in 5 countries.

Ehsan MotazediNORMENT Centre, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Weiqiu ChengNORMENT Centre, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Jesper Q ThomassenDepartment of Clinical Biochemistry, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
Oleksandr FreiNORMENT Centre, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Arvid RongveDepartment of Clinical Medicine, University of Bergen, Bergen, Norway.
Lavinia AthanasiuNORMENT Centre, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Shahram BahramiNORMENT Centre, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Alexey ShadrinNORMENT Centre, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Ingun UlsteinDepartment of Geriatric Medicine, Oslo University Hospital, Ullevål, Oslo, Norway.
Eystein StordalDepartment of Neuromedicine and Movement Science (INB), NTNU, Faculty of Medicine and Health Sciences, Trondheim, Norway.
Anne BrækhusDepartment of Geriatric Medicine, Oslo University Hospital, Ullevål, Oslo, Norway.
Ingvild SaltvedtDepartment of Neuromedicine and Movement Science (INB), NTNU, Faculty of Medicine and Health Sciences, Trondheim, Norway.
Sigrid B SandoDepartment of Neuromedicine and Movement Science (INB), NTNU, Faculty of Medicine and Health Sciences, Trondheim, Norway.
Kevin S O'ConnellNORMENT Centre, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Guy HindleyNORMENT Centre, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Dennis van der MeerNORMENT Centre, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Sverre BerghResearch Center for Age-related Functional Decline and Disease, Innlandet Hospital Trust, Brumunddal, Norway.
Børge G NordestgaardDepartment of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Anne Tybjærg-HansenDepartment of Clinical Biochemistry, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
Geir BråthenDepartment of Neuromedicine and Movement Science (INB), NTNU, Faculty of Medicine and Health Sciences, Trondheim, Norway.
Lasse PihlstrømDepartment of Neurology, Oslo University Hospital, Oslo, Norway.
Srdjan DjurovicDepartment of Medical Genetics, Oslo University Hospital, Oslo, Norway.
Ruth Frikke-SchmidtDepartment of Clinical Biochemistry, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
Tormod FladbyDepartment of Neuromedicine and Movement Science (INB), NTNU, Faculty of Medicine and Health Sciences, Trondheim, Norway.
Dag AarslandDepartment of Old-Age Psychiatry, Stavanger University Hospital, Stavanger, Norway.
Geir SelbækDepartment of Geriatric Medicine, Oslo University Hospital, Ullevål, Oslo, Norway.
Tyler M SeibertNORMENT Centre, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Anders M DaleCenter for Multimodal Imaging and Genetics, University of California San Diego, La Jolla, CA, USA.
Chun C FanCenter for Multimodal Imaging and Genetics, University of California San Diego, La Jolla, CA, USA.
Ole A AndreassenNORMENT Centre, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Oslo University Hospital · NOUniversity of Oslo · NORigshospitalet · DKNorwegian University of Science and Technology · NOSt Olav's University Hospital · NOUniversity of Bergen · NOUniversity of California, San Diego · USAkershus University Hospital · NOGentofte Hospital · DKKing's College London · GBSykehuset i Vestfold · NO

Funding

Spatiotemporal Brain Imaging: Microscopic &System LevelR01EB000790 · NIBIB · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DALE, ANDERS M · 2002 to 2015
$15.3M
VULNERABILITY, INTERVENING EVENTS &DISABILITY IN AGINGR01AG017560 · NIA · YALE UNIVERSITY · PI GILL, THOMAS MICHAEL · 2000 to 2025
$7.0M
Clarifying risk and protective factors for dementia with the Interplay of Genes and Environment in Multiple Studies (IGEMS) consortiumR01AG060470 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI GATZ, MARGARET, PEDERSEN, NANCY L · 2018 to 2022
$3.6M
Neuronal, glial and BOLD fMRI signals: From BOLD to 2-photon microscopyR01NS057198 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DEVOR, ANNA · 2009 to 2017
$2.6M
DEMENTIA IN TWINSR01AG008724 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI GATZ, MARGARET · 1990 to 2002
$1.4M
Cholesterol metabolism pathway: Cognitive change and Alzheimer's disease riskR01AG028555 · NIA · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI REYNOLDS, CHANDRA A · 2007 to 2010
$1.1M
Improving assessment of prostate cancer bone metastases using advanced diffusion imagingK08EB026503 · NIBIB · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SEIBERT, TYLER MICHAEL · 2019 to 2022
$805k
COGNITIVE DECLINE AND THE ROLE OF SPICIFIC GENESR01AG017561 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI REYNOLDS, CHANDRA A · 1999 to 2000
$96k
NIA NIH HHS R01 AG008724NIA NIH HHS R01 AG017560NIA NIH HHS R01 AG017561NIA NIH HHS R01 AG028555NIA NIH HHS R01 AG060470NIBIB NIH HHS K08 EB026503NIBIB NIH HHS R01 EB000790NINDS NIH HHS R01 NS057198
6 · The paper itself

Abstract

backgroundPolygenic hazard scores (PHS) estimate age-dependent genetic risk of late-onset Alzheimer's disease (AD), but there is limited information about the performance of PHS on real-world data where the population of interest differs from the model development population and part of the model genotypes are missing or need to be imputed.

objectiveThe aim of this study was to estimate age-dependent risk of late-onset AD using polygenic predictors in Nordic populations.

methodsWe used Desikan PHS model, based on Cox proportional hazards assumption, to obtain age-dependent hazard scores for AD from individual genotypes in the Norwegian DemGene cohort (n = 2,772). We assessed the risk discrimination and calibration of Desikan model and extended it by adding new genotype markers (the Desikan Nordic model). Finally, we evaluated both Desikan and Desikan Nordic models in two independent Danish cohorts: The Copenhagen City Heart Study (CCHS) cohort (n = 7,643) and The Copenhagen General Population Study (CGPS) cohort (n = 10,886).

resultsWe showed a robust prediction efficiency of Desikan model in stratifying AD risk groups in Nordic populations, even when some of the model SNPs were missing or imputed. We attempted to improve Desikan PHS model by adding new SNPs to it, but we still achieved similar risk discrimination and calibration with the extended model.

conclusionPHS modeling has the potential to guide the timing of treatment initiation based on individual risk profiles and can help enrich clinical trials with people at high risk to AD in Nordic populations.

Indexed as

Alzheimer DiseaseAge of OnsetGenotypeHumansMultifactorial InheritancePolymorphism, Single NucleotideAge at onsetAlzheimer’s diseaseNordic ancestrypolygenic hazard score

Identifiers

PMID35848024
PMCPMC10022308
OpenAlexW4285096128

What OpenQuestion 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 OpenQuestion graph.