SynthesisMolecular psychiatry2014
A genome-wide association meta-analysis of plasma Aβ peptides concentrations in the elderly.
Open access · bronzeAbstract readMeta-Analysis
In one paragraph
Synthesis in Molecular psychiatry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 1 pooled it
2.8field-weighted citation impact, top 10% of its field
What it found
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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.
The trial behind it
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- From Polygenic Scores to Precision Medicine in Alzheimer's Disease: A Systematic Review.Journal of Alzheimer's disease : JAD · 2020Pooled it
- The Association Between Alzheimer's Disease-Related Biomarkers And Parkinson's Disease Based On Single-Cell Sequencing Analysis Combined With Mendelian Randomization.Journal of molecular neuroscience : MN · 2026Article
- The heritability of blood-based biomarkers related to risk of Alzheimer's disease in a population-based sample of early old-age men.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- The Physiological and Pathological Role of Acyl-CoA Oxidation.International journal of molecular sciences · 2023Review
- Disturbance of phylogenetic layer-specific adaptation of human brain gene expression in Alzheimer's disease.Scientific reports · 2021Article
- Plasma amyloid β levels are driven by genetic variants near APOE, BACE1, APP, PSEN2: A genome-wide association study in over 12,000 non-demented participants.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2021Article
- Admixture mapping reveals the association between Native American ancestry at 3q13.11 and reduced risk of Alzheimer's disease in Caribbean Hispanics.Alzheimer's research & therapy · 2021Article
- Amyloid, tau and risk of Alzheimer's disease: a Mendelian randomization study.European journal of epidemiology · 2021Article
- Association of plasma β-amyloid 40 and 42 concentration with type 2 diabetes among Chinese adults.Diabetologia · 2020Article
- Using Multi-Scale Genetic, Neuroimaging and Clinical Data for Predicting Alzheimer's Disease and Reconstruction of Relevant Biological Mechanisms.Scientific reports · 2018Article
- QTL and systems genetics analysis of mouse grooming and behavioral responses to novelty in an open field.Genes, brain, and behavior · 2017Article
- Recent publications from the Alzheimer's Disease Neuroimaging Initiative: Reviewing progress toward improved AD clinical trials.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2017Review
- Article
- Association analysis of ANK3 gene variants with schizophrenia in a northern Chinese Han population.Oncotarget · 2016Article
- Molecular systems evaluation of oligomerogenic APP(E693Q) and fibrillogenic APP(KM670/671NL)/PSEN1(Δexon9) mouse models identifies shared features with human Alzheimer's brain molecular pathology.Molecular psychiatry · 2016Article
- Copy number variation associates with mortality in long-lived individuals: a genome-wide assessment.Aging cell · 2016Article
- Candidate genes for Alzheimer's disease are associated with individual differences in plasma levels of beta amyloid peptides in adults with Down syndrome.Neurobiology of aging · 2015Article
- Genetic studies of quantitative MCI and AD phenotypes in ADNI: Progress, opportunities, and plans.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2015Review
- Association between 5q23.2-located polymorphism of CTXN3 gene (Cortexin 3) and schizophrenia in European-Caucasian males; implications for the aetiology of schizophrenia.Behavioral and brain functions : BBF · 2015Article
- Review
Corrections and comments
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Authors and funding
31 authors at 6 institutions in 4 countries.
V Chouraki1] INSERM U744, Lille, France [2] Institut pasteur de Lille, Lille, France [3] Université Lille-Nord de France, Lille, France.
R F A G De Bruijn1] Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands [2] Department of Neurology, Erasmus MC University Medical Center, Rotterdam, The Netherlands [3] Netherlands Consortium for Healthy Aging, Leiden, The Netherlands.
J Chapuis1] INSERM U744, Lille, France [2] Institut pasteur de Lille, Lille, France [3] Université Lille-Nord de France, Lille, France.
J C BisCardiovascular Health Resarch Unit and Department of Medicine, University of Washington, Seattle, WA, USA.
C Reitz1] The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA [2] The Gertrude H. Sergievsky Center, Columbia University, New York, NY, USA [3] The Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
S Schraen1] Université Lille-Nord de France, Lille, France [2] Inserm U837, Jean-Pierre Aubert Research Centre, Lille, France [3] Centre Hospitalier Régional Universitaire de Lille, Lille, France.
C A Ibrahim-Verbaas1] Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands [2] Department of Neurology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
B Grenier-Boley1] INSERM U744, Lille, France [2] Institut pasteur de Lille, Lille, France [3] Université Lille-Nord de France, Lille, France.
C Delay1] INSERM U744, Lille, France [2] Institut pasteur de Lille, Lille, France [3] Université Lille-Nord de France, Lille, France.
R RogersThe Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA.
F Demiautte1] INSERM U744, Lille, France [2] Institut pasteur de Lille, Lille, France [3] Université Lille-Nord de France, Lille, France.
A Mounier1] INSERM U744, Lille, France [2] Institut pasteur de Lille, Lille, France [3] Université Lille-Nord de France, Lille, France.
A L FitzpatrickCardiovascular Health Resarch Unit and Department of Medicine, University of Washington, Seattle, WA, USA.
Alzheimer's Disease Neuroimaging Initiative
C BerrINSERM U888, Hôpital La Colombière, Montpellier, France.
J-F DartiguesINSERM U593, Victor Segalen University, Bordeaux, France.
A G Uitterlinden1] Netherlands Consortium for Healthy Aging, Leiden, The Netherlands [2] Department of Internal medicine, Leiden, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
A Hofman1] Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands [2] Netherlands Consortium for Healthy Aging, Leiden, The Netherlands.
M Breteler1] Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands [2] DZNE, German Center for Neurodegenerative Diseases, Bonn, Germany.
J T BeckerAlzheimer's Disease Research Center, Departments of Neurology, Psychiatry and Psychology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
M Lathrop1] Fondation Jean Dausset-Centre d'Etude du Polymorphisme Humain, Paris, France [2] Centre National de Genotypage, Institut Genomique, Commissariat à l'énergie Atomique, Evry, France.
N SchupfThe Gertrude H. Sergievsky Center, Columbia University, New York, NY, USA.
A AlpérovitchINSERM U708, Paris, France.
R Mayeux1] The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA [2] The Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
C M van Duijn1] Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands [2] Netherlands Consortium for Healthy Aging, Leiden, The Netherlands.
L Buée1] Université Lille-Nord de France, Lille, France [2] Inserm U837, Jean-Pierre Aubert Research Centre, Lille, France [3] Centre Hospitalier Régional Universitaire de Lille, Lille, France.
P Amouyel1] INSERM U744, Lille, France [2] Institut pasteur de Lille, Lille, France [3] Université Lille-Nord de France, Lille, France [4] Centre Hospitalier Régional Universitaire de Lille, Lille, France.
O L LopezAlzheimer's Disease Research Center, Departments of Neurology, Psychiatry and Psychology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
M A Ikram1] Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands [2] Department of Neurology, Erasmus MC University Medical Center, Rotterdam, The Netherlands [3] Netherlands Consortium for Healthy Aging, Leiden, The Netherlands [4] Department of Radiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
C Tzourio1] INSERM U593, Victor Segalen University, Bordeaux, France [2] INSERM U708, Paris, France.
J-C Lambert1] INSERM U744, Lille, France [2] Institut pasteur de Lille, Lille, France [3] Université Lille-Nord de France, Lille, France.
Inserm · FRErasmus MC · NLUniversity of Pittsburgh · USColumbia University · USUniversity of Washington · USFondation Jean Dausset-CEPH · FR
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
$119.8MRECRUITMENT COREU19AG010483 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FELDMAN, HOWARD · 2013 to 2020
$80.6MUCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0MSatellite Diagnostic and Treatment Clinic CoreP50AG008702 · NIA · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI DE JAGER, PHILIP L · 1989 to 2019
$46.3MTransgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Andrea L Hevener · 2003 to 2026
$40.4MUC Davis Alzheimer's Disease Core CenterP30AG010129 · NIA · UNIVERSITY OF CALIFORNIA DAVIS · PI DECARLI, CHARLES · 1991 to 2020
$28.3MVASCULAR FACTORS AND MILD COGNITIVE IMPAIRMENT AND ALZHEIMER'S DISEASEP01AG007232 · NIA · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI STERN, YAAKOV · 1989 to 2008
$21.7MEpidemiology of Biomarkers of Risk and Progression in LOADR01AG037212 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI MAYEUX, RICHARD P, SCHUPF, NICOLE · 2010 to 2015
$10.1MExceptional Survival: Trajectories to Functional Aging (CHS All Stars)R01AG023629 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI NEWMAN, ANNE B. · 2004 to 2016
$9.5MCHARGE Consortium: Omics Discovery for CVD and Aging PhenotypesR01HL105756 · NHLBI · UNIVERSITY OF WASHINGTON · PI Bruce M Psaty, NICHOLAS L SMITH · 2011 to 2026
$9.5MCHS Events Follow-up StudyR01HL080295 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M · 2009 to 2014
$6.3MWGA Study to Identify Genetic Variants Associated with CV Events in CHSR01HL087652 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M · 2007 to 2009
$5.1MNCATS NIH HHS UL1 TR000124NCATS NIH HHS UL1TR000124NHLBI NIH HHS HHSN268200800007CNHLBI NIH HHS HHSN268201200036CNHLBI NIH HHS HL080295NHLBI NIH HHS HL087652NHLBI NIH HHS HL105756NHLBI NIH HHS N01 HC055222NHLBI NIH HHS N01 HC085079NHLBI NIH HHS N01 HC085080NHLBI NIH HHS N01 HC085081NHLBI NIH HHS N01 HC085082NHLBI NIH HHS N01 HC085083NHLBI NIH HHS N01 HC085086NHLBI NIH HHS R01 HL080295NHLBI NIH HHS R01 HL087652NHLBI NIH HHS R01 HL105756NHLBI NIH HHS U01 HL080295NIA NIH HHS AG023629NIA NIH HHS K01 AG030514NIA NIH HHS K23 AG034550NIA NIH HHS P01 AG007232NIA NIH HHS P30 AG010129NIA NIH HHS P50 AG008702NIA NIH HHS R01 AG023629NIA NIH HHS R01 AG037212NIA NIH HHS R56 AG023629NIA NIH HHS U19 AG010483NIA NIH HHS U24 AG021886NIDDK NIH HHS DK063491NIDDK NIH HHS P30 DK063491
Abstract
Amyloid beta (Aβ) peptides are the major components of senile plaques, one of the main pathological hallmarks of Alzheimer disease (AD). However, Aβ peptides' functions are not fully understood and seem to be highly pleiotropic. We hypothesized that plasma Aβ peptides concentrations could be a suitable endophenotype for a genome-wide association study (GWAS) designed to (i) identify novel genetic factors involved in amyloid precursor protein metabolism and (ii) highlight relevant Aβ-related physiological and pathophysiological processes. Hence, we performed a genome-wide association meta-analysis of four studies totaling 3 528 healthy individuals of European descent and for whom plasma Aβ1-40 and Aβ1-42 peptides levels had been quantified. Although we did not observe any genome-wide significant locus, we identified 18 suggestive loci (P<1 × 10(-)(5)). Enrichment-pathway analyses revealed canonical pathways mainly involved in neuronal functions, for example, axonal guidance signaling. We also assessed the biological impact of the gene most strongly associated with plasma Aβ1-42 levels (cortexin 3, CTXN3) on APP metabolism in vitro and found that the gene protein was able to modulate Aβ1-42 secretion. In conclusion, our study results suggest that plasma Aβ peptides levels are valid endophenotypes in GWASs and can be used to characterize the metabolism and functions of APP and its metabolites.
Indexed as
AgingAmyloid beta-PeptidesAmyloid beta-Protein PrecursorGenome-Wide Association StudyHEK293 CellsHumansMembrane ProteinsPeptide FragmentsPolymorphism, Single NucleotideWhite PeopleAmyloid beta-Peptidesamyloid beta-protein (1-40)amyloid beta-protein (1-42)Amyloid beta-Protein PrecursorAPP protein, humanCTXN3 protein, humanMembrane ProteinsPeptide Fragments
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