Evidence map›Paper›PMID 25862742›Full record

SynthesisCirculation2015

Polygenic Overlap Between C-Reactive Protein, Plasma Lipids, and Alzheimer Disease.

Rahul S Desikan, Andrew J Schork, Yunpeng Wang, Wesley K Thompson, Abbas Dehghan, Paul M Ridker, Daniel I Chasman, Linda K McEvoy, Dominic Holland, Chi-Hua Chen and 38 more

Open access · greenAbstract readComparative StudyEvaluation StudyMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Circulation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
91citing papers in PubMed, 7 pooled it
14.8field-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

91 citing papers in PubMed, 7 syntheses or guidelines pooled it, 162 citations in OpenAlex.

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  10. Functional Analysis of Late-Onset Alzheimer's Disease Risk Genes inbioRxiv : the preprint server for biology · 2026
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31 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

48 authors at 7 institutions in 5 countries.

Rahul S DesikanDepartment of Radiology, University of California, San Diego, La Jolla, CA.
Andrew J Schork *Department of Cognitive Science, University of California, San Diego, La Jolla, CA.
Yunpeng Wang *Department of Neurosciences, University of California, San Diego, La Jolla, CA.
Wesley K ThompsonDepartment of Psychiatry, University of California, San Diego, La Jolla, CA.
Abbas DehghanDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, Netherlands.
Paul M RidkerCenter for Cardiovascular Disease Prevention, Division of Preventative Medicine, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA.
Daniel I ChasmanCenter for Cardiovascular Disease Prevention, Division of Preventative Medicine, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA.
Linda K McEvoyDepartment of Radiology, University of California, San Diego, La Jolla, CA.
Dominic HollandDepartment of Neurosciences, University of California, San Diego, La Jolla, CA.
Chi-Hua ChenDepartment of Radiology, University of California, San Diego, La Jolla, CA.
David S KarowDepartment of Radiology, University of California, San Diego, La Jolla, CA.
James B BrewerDepartment of Radiology, University of California, San Diego, La Jolla, CA.
Christopher P HessDepartment of Radiology and Biomedical Imaging, University of California, San Francisco, CA.
Julie WilliamsMedical Research Council Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Wales, United Kingdom.
Rebecca SimsMedical Research Council Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Wales, United Kingdom.
Michael C O'DonovanMedical Research Council Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Wales, United Kingdom.
Seung Hoan ChoiDepartment of Biostatistics, School of Public Health, Boston University, Boston, MA.
Joshua C BisDeparment of Internal Medicine, University of Washington, Seattle, WA.
M Arfan IkramDeparment of Epidemiology, Erasmus MC, Rotterdam, Netherlands.
Vilmundur GudnasonIcelandic Heart Association, Kopavogur, Iceland; Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
Anita L DeStefanoDepartment of Biostatistics, School of Public Health, Boston University, Boston, MA.
Sven J van der LeeDeparment of Epidemiology, Erasmus MC, Rotterdam, Netherlands.
Bruce M PsatyCardiovascular Health Research Unit, Departments of Medicine, Epidemiology and Health Services, University of Washington, Seattle, WA; Group Health Research Institute, Group Health Cooperative, Seattle, WA.
Cornelia M van DuijnDeparment of Epidemiology, Erasmus MC, Rotterdam, Netherlands.
Lenore LaunerLaboratory of Epidemiology, Demography and Biometry, Intramural Research Program, National Institute on Aging, Washington, DC.
Sudha SeshadriThe National Heart Lung and Blood Institute's Framingham Heart Study, Framingham, MA.
Margaret A Pericak-VanceThe John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL.
Richard MayeuxDepartment of Neurology, Taub Institute on Alzheimer's Disease and the Aging Brain, and Gertrude H. Sergievsky Center, Columbia University, New York, NY.
Jonathan L HainesDepartment of Epidemiology and Biostatistics and Institute for Computational Biology, Case Western University, Cleveland, OH.
Lindsay A FarrerDepartments of Medicine (Biomedical Genetics), Neurology, Ophthalmology, Biostatistics, and Epidemiology, Boston University Schools of Medicine and Public Health, Boston, MA.
John HardyDepartment of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom.
Ingun Dina UlsteinNorwegian Centre for Dementia Research, Department of Old Age Psychiatry, Oslo University Hospital, Oslo, Norway.
Dag AarslandDepartment of Cognitive Science, University of California, San Diego, La Jolla, CA.
Tormod FladbyInstitute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Neurology, Akershus University Hospital, Norway.
Linda R WhiteDepartment of Neuroscience, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
Sigrid B SandoDepartment of Neuroscience, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
Arvid RongveDepartment of Psychiatry, Haugesund Hospital, Haugesund, Norway.
Aree WitoelarNORMENT; Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Srdjan DjurovicDepartment of Medical Genetics, Oslo University Hospital, Oslo and NORMENT, KG Jebsen Centre for Psychosis Research; Department of Clinical Science, University of Bergen, Bergen, Norway.
Bradley T HymanDepartment of Neurology, Massachusetts General Hospital, Boston, MA.
Jon SnaedalDepartment of Geriatric Medicine, University Hospital Reykjavik, Iceland.
Stacy SteinbergdeCODE Genetics, Reykjavik, Iceland.
Hreinn StefanssondeCODE Genetics, Reykjavik, Iceland.
Kari StefanssondeCODE Genetics, Reykjavik, Iceland.
Gerard D SchellenbergDepartment of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
Ole A AndreassenNORMENT; Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Anders M DaleDepartment of Radiology, University of California, San Diego, La Jolla, CA.
Inflammation working group, IGAP and DemGene Investigators
University of Oslo · NOdeCODE Genetics (Iceland) · ISNational Institutes of Health · USInstitute on Aging · USPrivatsykehuset Haugesund · NOStavanger University Hospital · NOUniversity of Bergen · NO

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
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
THE ROLE OF ADVANCED CAA IN ALZHEIMER'S DEMENTIAP50AG005134 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI HYMAN, BRADLEY T. · 1985 to 2018
$42.1M
Research Education ComponentP30AG062421 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI Christine S Ritchie · 2019 to 2026
$36.5M
UPenn ADCC Biomarker CoreP30AG010124 · NIA · UNIVERSITY OF PENNSYLVANIA · PI XIE, SHARON XIANGWEN · 1991 to 2020
$35.1M
Neuropathology CoreP30AG013846 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI KOWALL, NEIL W. · 1996 to 2020
$29.1M
UC Davis Alzheimer's Disease Core CenterP30AG010129 · NIA · UNIVERSITY OF CALIFORNIA DAVIS · PI DECARLI, CHARLES · 1991 to 2020
$28.3M
PRECURSORS OF STROKE INCIDENCE AND PROGNOSISR01NS017950 · NINDS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Hugo Javier Aparicio, Jose Rafael Romero · 1985 to 2026
$22.9M
EPIDEMIOLOGY OF DEMENTIA IN THE FRAMINGHAM STUDYR01AG008122 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI AU, RHODA, SESHADRI, SUDHA · 1989 to 2015
$14.4M
CHARGE Consortium: Omics Discovery for CVD and Aging PhenotypesR01HL105756 · NHLBI · UNIVERSITY OF WASHINGTON · PI Bruce M Psaty, NICHOLAS L SMITH · 2011 to 2026
$9.5M
Creating a Pediatric Imaging-Genomics Data ResourceRC2DA029475 · NIDA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHANG, LINDA, DALE, ANDERS M · 2009 to 2011
$9.1M
Medical Research Council G0902227Medical Research Council MR/K013041/1Medical Research Council MR/L010305/1Medical Research Council MR/L023784/1Medical Research Council MR/L023784/2Medical Research Council MR/L501517/1NCI NIH HHS UM1 CA182913NHLBI NIH HHS R01 HL105756NIA NIH HHS AG033193NIA NIH HHS P30 AG010124NIA NIH HHS P30 AG010129NIA NIH HHS P30 AG013846NIA NIH HHS P30 AG062421NIA NIH HHS P50 AG005131NIA NIH HHS P50 AG005134NIA NIH HHS R01 AG008122NIA NIH HHS R01 AG015473NIA NIH HHS R01 AG031224NIA NIH HHS R01 AG033193NIA NIH HHS RF1 AG015473NIA NIH HHS U01 AG032984NIA NIH HHS U01 AG049505NIA NIH HHS U24 AG021886NIBIB NIH HHS T32 EB005970NICHD NIH HHS R01 HD061414NIDA NIH HHS RC2 DA029475NIGMS NIH HHS R01 GM104400NIGMS NIH HHS R01GM104400-01ANIMH NIH HHS R01 MH100351NIMH NIH HHS R01MH100351NINDS NIH HHS K02 NS067427NINDS NIH HHS R01 NS017950PHS HHS U0149505
6 · The paper itself

Abstract

backgroundEpidemiological findings suggest a relationship between Alzheimer disease (AD), inflammation, and dyslipidemia, although the nature of this relationship is not well understood. We investigated whether this phenotypic association arises from a shared genetic basis. METHODS AND

resultsUsing summary statistics (P values and odds ratios) from genome-wide association studies of >200 000 individuals, we investigated overlap in single-nucleotide polymorphisms associated with clinically diagnosed AD and C-reactive protein (CRP), triglycerides, and high- and low-density lipoprotein levels. We found up to 50-fold enrichment of AD single-nucleotide polymorphisms for different levels of association with C-reactive protein, low-density lipoprotein, high-density lipoprotein, and triglyceride single-nucleotide polymorphisms using a false discovery rate threshold <0.05. By conditioning on polymorphisms associated with the 4 phenotypes, we identified 55 loci associated with increased AD risk. We then conducted a meta-analysis of these 55 variants across 4 independent AD cohorts (total: n=29 054 AD cases and 114 824 healthy controls) and discovered 2 genome-wide significant variants on chromosome 4 (rs13113697; closest gene, HS3ST1; odds ratio=1.07; 95% confidence interval=1.05-1.11; P=2.86×10(-8)) and chromosome 10 (rs7920721; closest gene, ECHDC3; odds ratio=1.07; 95% confidence interval=1.04-1.11; P=3.38×10(-8)). We also found that gene expression of HS3ST1 and ECHDC3 was altered in AD brains compared with control brains.

conclusionsWe demonstrate genetic overlap between AD, C-reactive protein, and plasma lipids. By conditioning on the genetic association with the cardiovascular phenotypes, we identify novel AD susceptibility loci, including 2 genome-wide significant variants conferring increased risk for AD.

Indexed as

Genome-Wide Association StudyAgedAged, 80 and overAlzheimer DiseaseBiomarkersBrainC-Reactive ProteinDyslipidemiasFemaleHumansInflammationLipidsMaleMultifactorial InheritancePeroxisomal Bifunctional EnzymePhenotypeBiomarkersC-Reactive ProteinEHHADH protein, humanheparitin sulfotransferaseLipidsPeroxisomal Bifunctional EnzymeSulfotransferasesAlzheimer DiseaseGenome-Wide Association Studyinflammationlipids

Identifiers

PMID25862742
PMCPMC4677995
OpenAlexW2064257734

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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.