Evidence map›Paper›PMID 20697030›Full record

ArticleArchives of neurology2010

Meta-analysis confirms CR1, CLU, and PICALM as alzheimer disease risk loci and reveals interactions with APOE genotypes.

Gyungah Jun, Adam C Naj, Gary W Beecham, Li-San Wang, Jacqueline Buros, Paul J Gallins, Joseph D Buxbaum, Nilufer Ertekin-Taner, M Daniele Fallin, Robert Friedland and 27 more

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

Article in Archives of neurology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 249 papers, 12 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
249citing papers in PubMed, 12 pooled it
22.7field-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

249 citing papers in PubMed, 12 syntheses or guidelines pooled it, 427 citations in OpenAlex.

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  8. Smoking and increased Alzheimer's disease risk: a review of potential mechanisms.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2014
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189 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

37 authors at 1 institution in 1 country.

Gyungah JunDepartment of Medicine, Boston University, USA.
Adam C Naj
Gary W Beecham
Li-San Wang
Jacqueline Buros
Paul J Gallins
Joseph D Buxbaum
Nilufer Ertekin-Taner
M Daniele Fallin
Robert Friedland
Rivka Inzelberg
Patricia Kramer
Ekaterina Rogaeva
Peter St George-Hyslop
Alzheimer's Disease Genetics Consortium
Laura B Cantwell
Beth A Dombroski
Andrew J Saykin
Eric M Reiman
David A Bennett
John C Morris
Kathryn L Lunetta
Eden R Martin
Thomas J Montine
Alison M Goate
Deborah Blacker
Debby W Tsuang
Duane Beekly
L Adrienne Cupples
Hakon Hakonarson
Walter Kukull
Tatiana M Foroud
Jonathan Haines
Richard Mayeux
Lindsay A Farrer
Margaret A Pericak-Vance
Gerard D Schellenberg
Boston University · US

Funding

Alzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0M
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
TRIAL OF VALPROATE TO ATTENUATE THE PROGRESSION OF ADU01AG010483 · NIA · UNIVERSITY OF ROCHESTER · PI AISEN, PAUL S. · 1991 to 2012
$116.2M
RECRUITMENT COREU19AG010483 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FELDMAN, HOWARD · 2013 to 2020
$80.6M
NATIONAL ALZHEIMERS COORDINATING CENTER (NACC)U01AG016976 · NIA · UNIVERSITY OF WASHINGTON · PI KUKULL, WALTER ANTHONY · 1999 to 2020
$72.8M
Smartphone-Based "Burst" Cognitive AssessmentsP01AG003991 · NIA · WASHINGTON UNIVERSITY · PI Tammie Lee Smith Benzinger · 1985 to 2026
$69.5M
TDP-43 Loss-of-Function: Biology to BiomarkersP01AG019724 · NIA · UNIVERSITY OF PENNSYLVANIA · PI Jennifer Merrilees · 2002 to 2026
$67.2M
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 JAYADEY, SUMAN · 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 MORRIS, JOHN · 1985 to 2019
$52.1M
SUPPLEMENT TO ALZHEIMERS DISEASE PATIENT REGISTRYU01AG006786 · NIA · MAYO CLINIC ROCHESTER · PI GRAFF-RADFORD, JONATHAN, JACK, CLIFFORD R. · 1986 to 2023
$49.6M
NCI NIH HHS R01 CA129769NCI NIH HHS U54 CA132378NCI NIH HHS U54 CA137788NCRR NIH HHS M01 RR000096NCRR NIH HHS MO1 RR00096NCRR NIH HHS UL1 RR025777NCRR NIH HHS UL1 RR02777NCRR NIH HHS UL1 RR029893NHGRI NIH HHS R01 HG002213NHGRI NIH HHS R01 HG02213NHGRI NIH HHS U01 HG006375NHLBI NIH HHS N01 HC025195NHLBI NIH HHS N01 HC-25195NIA NIH HHS AG002219NIA NIH HHS AG005138NIA NIH HHS AG010491NIA NIH HHS AG019757NIA NIH HHS AG021547NIA NIH HHS AG025688NIA NIH HHS AG027944NIA NIH HHS K01 AG030514NIA NIH HHS K24 AG027841NIA NIH HHS P01 AG002219NIA NIH HHS P01 AG003991NIA NIH HHS P01 AG010491NIA NIH HHS P01 AG019724NIA NIH HHS P01 AG03991NIA 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 AG028377NIA NIH HHS P30 AG028383NIA NIH HHS P30 AG08051NIA NIH HHS P30 AG10129NIA NIH HHS P30 AG10133NIA NIH HHS P30 AG10161NIA 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 AG008671NIA NIH HHS P50 AG008702NIA NIH HHS P50 AG016570NIA NIH HHS P50 AG016573NIA NIH HHS P50 AG016574NIA NIH HHS P50 AG016575NIA NIH HHS P50 AG016576NIA NIH HHS P50 AG016577NIA NIH HHS P50 AG016582NIA NIH HHS P50 AG023501NIA NIH HHS P50 AG025688NIA NIH HHS P50 AG05131NIA NIH HHS P50 AG05681NIA NIH HHS P50 AG08671NIA NIH HHS P50 AG16574NIA NIH HHS R01 AG008122NIA NIH HHS R01 AG009029NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG016495NIA NIH HHS R01 AG017173NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG019085NIA NIH HHS R01 AG019757NIA NIH HHS R01 AG020688NIA NIH HHS R01AG020688NIA NIH HHS R01 AG021547NIA NIH HHS R01 AG025259NIA NIH HHS R01 AG026916NIA NIH HHS R01 AG 027944NIA NIH HHS R01 AG027944NIA NIH HHS R01 AG030146NIA NIH HHS R01 AG031287NIA NIH HHS R01 AG031581NIA NIH HHS R01 AG032990NIA NIH HHS R01 AG033193NIA NIH HHS R01 AG037212NIA NIH HHS R01 AG041797NIA NIH HHS R01 AG08122NIA NIH HHS R01 AG16495NIA NIH HHS R01 AG17917NIA NIH HHS R37 AG015473NIA NIH HHS RC2 AG036528NIA NIH HHS RC2AG036528NIA NIH HHS RC2 AG036535NIA NIH HHS U01 AG006786NIA NIH HHS U01 AG010483NIA NIH HHS U01 AG016976NIA NIH HHS U01 AG024904NIA NIH HHS U01 AG032984NIA NIH HHS U01AG06786NIA NIH HHS U01 AG10483NIA NIH HHS U19 AG010483NIA NIH HHS U24 AG021886NIA NIH HHS U24-AG021886NIA NIH HHS U24 AG026395NIA NIH HHS U24 AG056270NIA NIH HHS UO1 AG16976NIMH NIH HHS R01 MH080295NINDS NIH HHS K08 NS054811NINDS NIH HHS R01 NS017950Wellcome Trust 081864
6 · The paper itself

Abstract

objectivesTo determine whether genotypes at CLU, PICALM, and CR1 confer risk for Alzheimer disease (AD) and whether risk for AD associated with these genes is influenced by apolipoprotein E (APOE) genotypes.

designAssociation study of AD and CLU, PICALM, CR1, and APOE genotypes.

settingAcademic research institutions in the United States, Canada, and Israel.

participantsSeven thousand seventy cases with AD, 3055 with autopsies, and 8169 elderly cognitively normal controls, 1092 with autopsies, from 12 different studies, including white, African American, Israeli-Arab, and Caribbean Hispanic individuals.

resultsUnadjusted, CLU (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.85-0.96 for single-nucleotide polymorphism [SNP] rs11136000), CR1 (OR, 1.14; 95% CI, 1.07-1.22; SNP rs3818361), and PICALM (OR, 0.89; 95% CI, 0.84-0.94, SNP rs3851179) were associated with AD in white individuals. None were significantly associated with AD in the other ethnic groups. APOE ε4 was significantly associated with AD (ORs, 1.80-9.05) in all but 1 small white cohort and in the Arab cohort. Adjusting for age, sex, and the presence of at least 1 APOE ε4 allele greatly reduced evidence for association with PICALM but not CR1 or CLU. Models with the main SNP effect, presence or absence of APOE ε4, and an interaction term showed significant interaction between presence or absence of APOE ε4 and PICALM.

conclusionsWe confirm in a completely independent data set that CR1, CLU, and PICALM are AD susceptibility loci in European ancestry populations. Genotypes at PICALM confer risk predominantly in APOE ε4-positive subjects. Thus, APOE and PICALM synergistically interact.

Indexed as

AgedAged, 80 and overAlzheimer DiseaseApolipoproteins EClusterinCohort StudiesConfidence IntervalsFemaleGene FrequencyGenome-Wide Association StudyGenotypeHumansMaleMeta-Analysis as TopicMonomeric Clathrin Assembly ProteinsOdds RatioApolipoproteins ECLU protein, humanClusterinCR1 protein, humanMonomeric Clathrin Assembly ProteinsPICALM protein, humanReceptors, Complement 3b

Identifiers

PMID20697030
PMCPMC3048805
OpenAlexW2171610997

What OpenQuestion holds

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Read underepoch 390

Registered trials

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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.