Evidence map›Paper›PMID 27088644›Full record

ArticleJAMA neurology2016

Association Between Genetic Traits for Immune-Mediated Diseases and Alzheimer Disease.

Jennifer S Yokoyama, Yunpeng Wang, Andrew J Schork, Wesley K Thompson, Celeste M Karch, Carlos Cruchaga, Linda K McEvoy, Aree Witoelar, Chi-Hua Chen, Dominic Holland and 19 more

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

Article in JAMA neurology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
118citing papers in PubMed, 4 pooled it
6.7field-weighted citation impact, top 2% 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

118 citing papers in PubMed, 4 syntheses or guidelines pooled it, 185 citations in OpenAlex.

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58 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

29 authors at 8 institutions in 3 countries.

Jennifer S YokoyamaDepartment of Neurology, University of California, San Francisco.
Yunpeng WangDepartment of Psychiatry, Washington University, St Louis, Missouri3Department of Neurosciences, University of California, San Diego, La Jolla.
Andrew J SchorkDepartment of Cognitive Sciences, University of California, San Diego, La Jolla.
Wesley K ThompsonDepartment of Psychiatry, University of California, San Diego, La Jolla.
Celeste M KarchDepartment of Psychiatry, Washington University, St Louis, Missouri.
Carlos CruchagaDepartment of Psychiatry, Washington University, St Louis, Missouri.
Linda K McEvoyDepartment of Radiology, University of California, San Diego, La Jolla.
Aree WitoelarNorwegian Centre for Mental Disorders Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway8Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Chi-Hua ChenDepartment of Radiology, University of California, San Diego, La Jolla.
Dominic HollandDepartment of Neurosciences, University of California, San Diego, La Jolla.
James B BrewerDepartment of Neurosciences, University of California, San Diego, La Jolla6Department of Radiology, University of California, San Diego, La Jolla.
Andre FrankeInstitute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
William P DillonNeuroradiology Section, Department of Radiology and Biomedical Imaging, University of California, San Francisco.
David M WilsonNeuroradiology Section, Department of Radiology and Biomedical Imaging, University of California, San Francisco.
Pratik MukherjeeNeuroradiology Section, Department of Radiology and Biomedical Imaging, University of California, San Francisco.
Christopher P HessNeuroradiology Section, Department of Radiology and Biomedical Imaging, University of California, San Francisco.
Zachary MillerDepartment of Neurology, University of California, San Francisco.
Luke W BonhamDepartment of Neurology, University of California, San Francisco.
Jeffrey ShenDepartment of Neurology, University of California, San Francisco.
Gil D RabinoviciDepartment of Neurology, University of California, San Francisco.
Howard J RosenDepartment of Neurology, University of California, San Francisco.
Bruce L MillerDepartment of Neurology, University of California, San Francisco.
Bradley T HymanDepartment of Neurology, Massachusetts General Hospital, Boston.
Gerard D SchellenbergDepartment of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia.
Tom H KarlsenNorwegian PSC Research Center and KG Jebsen Inflammation Research Centre, Research Institute of Internal Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway14Division of Gastroenterolog.
Ole A AndreassenNorwegian Centre for Mental Disorders Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway8Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Anders M DaleDepartment of Neurosciences, University of California, San Diego, La Jolla4Department of Cognitive Sciences, University of California, San Diego, La Jolla5Department of Psychiatry, University of California, San Diego, La Jolla6Department of Radiology, Uni.
Rahul S DesikanNeuroradiology Section, Department of Radiology and Biomedical Imaging, University of California, San Francisco.
Alzheimer’s Disease Neuroimaging Initiative
University of California, San Francisco · USUniversity of California, San Diego · USWashington University in St. Louis · USOslo University Hospital · NOKiel University · DEMassachusetts General Hospital · USUniversity of Oslo · NOUniversity of Pennsylvania · US

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
$119.8M
NATIONAL ALZHEIMERS COORDINATING CENTER (NACC)U01AG016976 · NIA · UNIVERSITY OF WASHINGTON · PI KUKULL, WALTER ANTHONY · 1999 to 2020
$72.8M
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
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
THE NIA GENETICS OF ALZHEIMER'S DISEASE DATA STORAGE SITEU24AG041689 · NIA · UNIVERSITY OF PENNSYLVANIA · PI LI-SAN WANG · 2012 to 2026
$42.3M
UPenn ADCC Biomarker CoreP30AG010124 · NIA · UNIVERSITY OF PENNSYLVANIA · PI XIE, SHARON XIANGWEN · 1991 to 2020
$35.1M
PrPSc SPECIFIC INTERACTION WITH NOVEL PrP-Fc FUSION PROTEINSP50AG023501 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MILLER, BRUCE L · 2004 to 2018
$27.1M
Creating a Pediatric Imaging-Genomics Data ResourceRC2DA029475 · NIDA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHANG, LINDA, DALE, ANDERS M · 2009 to 2011
$9.1M
Genome Wide associate analysis of Alzheimer's DiseaseRC2AG036528 · NIA · UNIVERSITY OF PENNSYLVANIA · PI SCHELLENBERG, GERARD DAVID · 2009 to 2010
$5.4M
Mapping Individual Cognitive Differences to Neural Variance and School ReadinessR01HD061414 · NICHD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JERNIGAN, TERRY L. · 2010 to 2014
$3.3M
NIA NIH HHS K01 AG046374NIA NIH HHS K01 AG049152NIA NIH HHS K24 AG045333NIA NIH HHS P01 AG019724NIA NIH HHS P30 AG010124NIA NIH HHS P50 AG005131NIA NIH HHS P50 AG005681NIA NIH HHS P50 AG023501NIA NIH HHS R01 AG045611NIA NIH HHS RC2 AG036528NIA NIH HHS U01 AG016976NIA NIH HHS U01 AG032984NIA NIH HHS U24 AG021886NIA NIH HHS U24 AG041689NICHD NIH HHS R01 HD061414NIDA NIH HHS RC2 DA029475NIGMS NIH HHS R01 GM104400
6 · The paper itself

Abstract

importanceLate-onset Alzheimer disease (AD), the most common form of dementia, places a large burden on families and society. Although epidemiological and clinical evidence suggests a relationship between inflammation and AD, their relationship is not well understood and could have implications for treatment and prevention strategies.

objectiveTo determine whether a subset of genes involved with increased risk of inflammation are also associated with increased risk for AD. DESIGN, SETTING, AND

participantsIn a genetic epidemiology study conducted in July 2015, we systematically investigated genetic overlap between AD (International Genomics of Alzheimer's Project stage 1) and Crohn disease, ulcerative colitis, rheumatoid arthritis, type 1 diabetes, celiac disease, and psoriasis using summary data from genome-wide association studies at multiple academic clinical research centers. P values and odds ratios from genome-wide association studies of more than 100 000 individuals were from previous comparisons of patients vs respective control cohorts. Diagnosis for each disorder was previously established for the parent study using consensus criteria. MAIN OUTCOMES AND MEASURES: The primary outcome was the pleiotropic (conjunction) false discovery rate P value. Follow-up for candidate variants included neuritic plaque and neurofibrillary tangle pathology; longitudinal Alzheimer's Disease Assessment Scale cognitive subscale scores as a measure of cognitive dysfunction (Alzheimer's Disease Neuroimaging Initiative); and gene expression in AD vs control brains (Gene Expression Omnibus data).

resultsEight single-nucleotide polymorphisms (false discovery rate P < .05) were associated with both AD and immune-mediated diseases. Of these, rs2516049 (closest gene HLA-DRB5; conjunction false discovery rate P = .04 for AD and psoriasis, 5.37 × 10-5 for AD, and 6.03 × 10-15 for psoriasis) and rs12570088 (closest gene IPMK; conjunction false discovery rate P = .009 for AD and Crohn disease, P = 5.73 × 10-6 for AD, and 6.57 × 10-5 for Crohn disease) demonstrated the same direction of allelic effect between AD and the immune-mediated diseases. Both rs2516049 and rs12570088 were significantly associated with neurofibrillary tangle pathology (P = .01352 and .03151, respectively); rs2516049 additionally correlated with longitudinal decline on Alzheimer's Disease Assessment Scale cognitive subscale scores (β [SE], 0.405 [0.190]; P = .03). Regarding gene expression, HLA-DRA and IPMK transcript expression was significantly altered in AD brains compared with control brains (HLA-DRA: β [SE], 0.155 [0.024]; P = 1.97 × 10-10; IPMK: β [SE], -0.096 [0.013]; P = 7.57 × 10-13). CONCLUSIONS AND RELEVANCE: Our findings demonstrate genetic overlap between AD and immune-mediated diseases and suggest that immune system processes influence AD pathogenesis and progression.

Indexed as

Alzheimer DiseaseCognition DisordersFemaleGenome-Wide Association StudyHLA-DRB5 ChainsHumansInflammationMalePhosphotransferases (Alcohol Group Acceptor)Polymorphism, Single NucleotideHLA-DRB5 Chainsinositol polyphosphate multikinasePhosphotransferases (Alcohol Group Acceptor)

Identifiers

PMID27088644
PMCPMC4905783
OpenAlexW2339196082

What OpenQuestion holds

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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 OpenQuestion graph.