Evidence map›Paper›PMID 27371493›Full record

ArticleNeurology2016

Relation of genomic variants for Alzheimer disease dementia to common neuropathologies.

Jose M Farfel, Lei Yu, Aron S Buchman, Julie A Schneider, Philip L De Jager, David A Bennett

Abstract read
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In one paragraph

Article in Neurology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed, 2 pooled it
–field-weighted citation impact
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

47 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
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  13. Pathological Roles of INPP5D in Alzheimer's Disease.Advances in experimental medicine and biology · 2023
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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

6 authors.

Jose M FarfelFrom the Department of Geriatrics (J.M.F.), University of Sao Paulo Medical School, Brazil; Department of Pathology (J.M.F., J.A.S.), Rush Alzheimer's Disease Center (J.M.F., L.Y., A.S.B., J.A.S., D.A.B.), and Department of Neurological Sciences (L.Y., A.S.B., J.A.S., D.A.B.), Rush University Medical Center, Chicago, IL; Program in Translational NeuroPsychiatric Genomics (P.L.D.), Institute for the Neurosciences, Departments of Neurology and Psychiatry, Brigham and Women's Hospital, Boston; Harvard Medical School (P.L.D.), Boston; and Program in Medical and Population Genetics (P.L.D.), Broad Institute, Cambridge, MA. farfel@usp.br.
Lei YuFrom the Department of Geriatrics (J.M.F.), University of Sao Paulo Medical School, Brazil; Department of Pathology (J.M.F., J.A.S.), Rush Alzheimer's Disease Center (J.M.F., L.Y., A.S.B., J.A.S., D.A.B.), and Department of Neurological Sciences (L.Y., A.S.B., J.A.S., D.A.B.), Rush University Medical Center, Chicago, IL; Program in Translational NeuroPsychiatric Genomics (P.L.D.), Institute for the Neurosciences, Departments of Neurology and Psychiatry, Brigham and Women's Hospital, Boston; Harvard Medical School (P.L.D.), Boston; and Program in Medical and Population Genetics (P.L.D.), Broad Institute, Cambridge, MA.
Aron S BuchmanFrom the Department of Geriatrics (J.M.F.), University of Sao Paulo Medical School, Brazil; Department of Pathology (J.M.F., J.A.S.), Rush Alzheimer's Disease Center (J.M.F., L.Y., A.S.B., J.A.S., D.A.B.), and Department of Neurological Sciences (L.Y., A.S.B., J.A.S., D.A.B.), Rush University Medical Center, Chicago, IL; Program in Translational NeuroPsychiatric Genomics (P.L.D.), Institute for the Neurosciences, Departments of Neurology and Psychiatry, Brigham and Women's Hospital, Boston; Harvard Medical School (P.L.D.), Boston; and Program in Medical and Population Genetics (P.L.D.), Broad Institute, Cambridge, MA.
Julie A SchneiderFrom the Department of Geriatrics (J.M.F.), University of Sao Paulo Medical School, Brazil; Department of Pathology (J.M.F., J.A.S.), Rush Alzheimer's Disease Center (J.M.F., L.Y., A.S.B., J.A.S., D.A.B.), and Department of Neurological Sciences (L.Y., A.S.B., J.A.S., D.A.B.), Rush University Medical Center, Chicago, IL; Program in Translational NeuroPsychiatric Genomics (P.L.D.), Institute for the Neurosciences, Departments of Neurology and Psychiatry, Brigham and Women's Hospital, Boston; Harvard Medical School (P.L.D.), Boston; and Program in Medical and Population Genetics (P.L.D.), Broad Institute, Cambridge, MA.
Philip L De JagerFrom the Department of Geriatrics (J.M.F.), University of Sao Paulo Medical School, Brazil; Department of Pathology (J.M.F., J.A.S.), Rush Alzheimer's Disease Center (J.M.F., L.Y., A.S.B., J.A.S., D.A.B.), and Department of Neurological Sciences (L.Y., A.S.B., J.A.S., D.A.B.), Rush University Medical Center, Chicago, IL; Program in Translational NeuroPsychiatric Genomics (P.L.D.), Institute for the Neurosciences, Departments of Neurology and Psychiatry, Brigham and Women's Hospital, Boston; Harvard Medical School (P.L.D.), Boston; and Program in Medical and Population Genetics (P.L.D.), Broad Institute, Cambridge, MA.
David A BennettFrom the Department of Geriatrics (J.M.F.), University of Sao Paulo Medical School, Brazil; Department of Pathology (J.M.F., J.A.S.), Rush Alzheimer's Disease Center (J.M.F., L.Y., A.S.B., J.A.S., D.A.B.), and Department of Neurological Sciences (L.Y., A.S.B., J.A.S., D.A.B.), Rush University Medical Center, Chicago, IL; Program in Translational NeuroPsychiatric Genomics (P.L.D.), Institute for the Neurosciences, Departments of Neurology and Psychiatry, Brigham and Women's Hospital, Boston; Harvard Medical School (P.L.D.), Boston; and Program in Medical and Population Genetics (P.L.D.), Broad Institute, Cambridge, MA.

Funding

SUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1991 to 2020
$49.1M
EPIDEMIOLOGY OF NEURAL RESERVE AND NEUROBIOLOGY IN AGINGR01AG017917 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2001 to 2023
$43.3M
RISK FACTORS, PATHOLOGY, AND CLINICAL EXPRESSIONS OF ADR01AG015819 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1998 to 2024
$21.4M
Pathway discovery, validation and compound identification for Alzheimer's disease - SupplementU01AG046152 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BENNETT, DAVID ALAN, DE JAGER, PHILIP L · 2013 to 2017
$13.6M
Risk Factors, Pathology, and Clinical Expressions of ADRF1AG015819 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2014 to 2014
$6.0M
Epidemiologic Study of TDP-43 Pathology in Aging and DementiaR01AG042210 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI SCHNEIDER, JULIE A. · 2012 to 2018
$2.4M
NIA NIH HHS P30 AG010161NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG042210NIA NIH HHS RF1 AG015819NIA NIH HHS U01 AG046152
6 · The paper itself

Abstract

objectiveTo investigate the associations of previously reported Alzheimer disease (AD) dementia genomic variants with common neuropathologies.

methodsThis is a postmortem study including 1,017 autopsied participants from 2 clinicopathologic cohorts. Analyses focused on 22 genomic variants associated with AD dementia in large-scale case-control genome-wide association study (GWAS) meta-analyses. The neuropathologic traits of interest were a pathologic diagnosis of AD according to NIA-Reagan criteria, macroscopic and microscopic infarcts, Lewy bodies (LB), and hippocampal sclerosis. For each variant, multiple logistic regression was used to investigate its association with neuropathologic traits, adjusting for age, sex, and subpopulation structure. We also conducted power analyses to estimate the sample sizes required to detect genome-wide significance (p < 5 × 10(-8)) for pathologic AD for all variants.

resultsAPOE ε4 allele was associated with greater odds of pathologic AD (odds ratio [OR] 3.82, 95% confidence interval [CI] 2.67-5.46, p = 1.9 × 10(-13)), while ε2 allele was associated with lower odds of pathologic AD (OR 0.42, 95% CI 0.30-0.61, p = 3.1 × 10(-6)). Four additional genomic variants including rs6656401 (CR1), rs1476679 (ZCWPW1), rs35349669 (INPP5D), and rs17125944 (FERMT2) had p values less than 0.05. Remarkably, half of the previously reported AD dementia variants are not likely to be detected for association with pathologic AD with a sample size in excess of the largest GWAS meta-analyses of AD dementia.

conclusionsMany recently discovered genomic variants for AD dementia are not associated with the pathology of AD. Some genomic variants for AD dementia appear to be associated with other common neuropathologies.

Indexed as

Genetic VariationAged, 80 and overAllelesAlzheimer DiseaseApolipoproteins ECerebral InfarctionFemaleGenome, HumanGenome-Wide Association StudyHippocampusHumansLewy BodiesLogistic ModelsMaleMembrane ProteinsNeoplasm ProteinsApolipoproteins ECR1 protein, humanFERMT3 protein, humanINPP5D protein, humanMembrane ProteinsNeoplasm ProteinsPhosphatidylinositol-3,4,5-Trisphosphate 5-PhosphatasesReceptors, Complement 3b

Identifiers

PMID27371493
PMCPMC4970661

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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.