Evidence map›Paper›PMID 25853426›Full record

ArticlePloS one2015

Abundant genetic overlap between blood lipids and immune-mediated diseases indicates shared molecular genetic mechanisms.

Ole A Andreassen, Rahul S Desikan, Yunpeng Wang, Wesley K Thompson, Andrew J Schork, Verena Zuber, Nadezhda T Doncheva, Eva Ellinghaus, Mario Albrecht, Morten Mattingsdal and 9 more

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

Article in PloS one, 2015. 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 33 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed, 2 pooled it
4.2field-weighted citation impact, top 5% 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

33 citing papers in PubMed, 2 syntheses or guidelines pooled it, 44 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
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  11. Shared genetic etiology underlying late-onset Alzheimer's disease and posttraumatic stress syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2020
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  19. Potentiation of Psoriasis-Like Inflammation by PCSK9.The Journal of investigative dermatology · 2019
    Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 6 institutions in 4 countries.

Ole A AndreassenNORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, 0407 Oslo, Norway; Department of Psychiatry, University of California San Diego, La Jolla, CA 92093, United States of America.
Rahul S DesikanMultimodal Imaging Laboratory, University of California San Diego, La Jolla, CA 92093, United States of America; Department of Radiology, University of California San Diego, La Jolla, CA 92093, United States of America.
Yunpeng WangNORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, 0407 Oslo, Norway; Multimodal Imaging Laboratory, University of California San Diego, La Jolla, CA 92093, United States of America; Department of Neurosciences, University of California San Diego, La Jolla, CA 92093, United States of America.
Wesley K ThompsonDepartment of Psychiatry, University of California San Diego, La Jolla, CA 92093, United States of America.
Andrew J SchorkMultimodal Imaging Laboratory, University of California San Diego, La Jolla, CA 92093, United States of America; Cognitive Sciences Graduate Program, University of California San Diego, La Jolla, CA 92093, United States of America; Center for Human Development, University of California San Diego, La Jolla, CA 92093, United States of America.
Verena ZuberNORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, 0407 Oslo, Norway; Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo and Oslo University Hospital, 0407 Oslo, Norway.
Nadezhda T DonchevaMax Planck Institute for Informatics, 66123 Saarbrücken, Germany.
Eva EllinghausInstitute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, 24118 Kiel, Germany.
Mario AlbrechtMax Planck Institute for Informatics, 66123 Saarbrücken, Germany; Department of Bioinformatics, Institute of Biometrics and Medical Informatics, University Medicine Greifswald, 17475 Greifswald, Germany; Institute for Knowledge Discovery, Graz University of Technology, 8010 Graz, Austria; BioTechMed-Graz, 8010 Graz, Austria.
Morten MattingsdalNORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, 0407 Oslo, Norway; Sørlandet Hospital, 3000 Kristiansand, Norway.
Andre FrankeInstitute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, 24118 Kiel, Germany.
Benedicte A LieBioTechMed-Graz, 8010 Graz, Austria.
Ian G Mills
Ian MillsCentre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo and Oslo University Hospital, 0407 Oslo, Norway; Department of Cancer Prevention, Institute of Cancer Research and Department of Urology, Oslo University Hospital, 0407 Oslo, Norway.
Pål AukrustDepartment of Medical Genetics, University of Oslo and Oslo University Hospital, 0407 Oslo, Norway; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, 0407 Oslo Norway.
Linda K McEvoyMultimodal Imaging Laboratory, University of California San Diego, La Jolla, CA 92093, United States of America; Department of Radiology, University of California San Diego, La Jolla, CA 92093, United States of America.
Srdjan DjurovicNORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, 0407 Oslo, Norway; Department of Medical Genetics, University of Oslo and Oslo University Hospital, 0407 Oslo, Norway.
Tom H KarlsenK.G.Jebsen Inflammation Research Centre, Research Institute of Internal Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital Rikshospitalet, 0407 Oslo, Norway; Division of Gastroenterology, Institute of Medicine, University of Bergen, 5000 Bergen, Norway; Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital Rikshospitalet, 0407 Oslo, Norway.
Anders M DaleDepartment of Psychiatry, University of California San Diego, La Jolla, CA 92093, United States of America; Multimodal Imaging Laboratory, University of California San Diego, La Jolla, CA 92093, United States of America; Department of Radiology, University of California San Diego, La Jolla, CA 92093, United States of America; Department of Neurosciences, University of California San Diego, La Jolla, CA 92093, United States of America.
Oslo University Hospital · NOUniversity of California San Diego · USChristian-Albrechts-Universität zu Kiel · DEBioTechMed-Graz · ATMax Planck Institute for Informatics · DEUniversitätsmedizin Greifswald · DE

Funding

Polygenicity, Pleiotrophy and Power: Novel Statistical Methods for Gene DiscoveryR01GM104400 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI THOMPSON, WESLEY KURT · 2014 to 2017
$1.6M
NIGMS NIH HHS R01 GM104400
6 · The paper itself

Abstract

Epidemiological studies suggest a relationship between blood lipids and immune-mediated diseases, but the nature of these associations is not well understood. We used genome-wide association studies (GWAS) to investigate shared single nucleotide polymorphisms (SNPs) between blood lipids and immune-mediated diseases. We analyzed data from GWAS (n~200,000 individuals), applying new False Discovery Rate (FDR) methods, to investigate genetic overlap between blood lipid levels [triglycerides (TG), low density lipoproteins (LDL), high density lipoproteins (HDL)] and a selection of archetypal immune-mediated diseases (Crohn's disease, ulcerative colitis, rheumatoid arthritis, type 1 diabetes, celiac disease, psoriasis and sarcoidosis). We found significant polygenic pleiotropy between the blood lipids and all the investigated immune-mediated diseases. We discovered several shared risk loci between the immune-mediated diseases and TG (n = 88), LDL (n = 87) and HDL (n = 52). Three-way analyses differentiated the pattern of pleiotropy among the immune-mediated diseases. The new pleiotropic loci increased the number of functional gene network nodes representing blood lipid loci by 40%. Pathway analyses implicated several novel shared mechanisms for immune pathogenesis and lipid biology, including glycosphingolipid synthesis (e.g. FUT2) and intestinal host-microbe interactions (e.g. ATG16L1). We demonstrate a shared genetic basis for blood lipids and immune-mediated diseases independent of environmental factors. Our findings provide novel mechanistic insights into dyslipidemia and immune-mediated diseases and may have implications for therapeutic trials involving lipid-lowering and anti-inflammatory agents.

Indexed as

Autoimmune DiseasesGenetic LociGenetic PleiotropyGenome-Wide Association StudyHistocompatibility Antigens Class IHistocompatibility Antigens Class IIHumansInflammatory Bowel DiseasesLipoproteins, HDLLipoproteins, LDLPolymorphism, Single NucleotideTriglyceridesHistocompatibility Antigens Class IHistocompatibility Antigens Class IILipoproteins, HDLLipoproteins, LDLTriglycerides

Identifiers

PMID25853426
PMCPMC4390360
OpenAlexW1966073296

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.