Evidence map›Paper›PMID 25338677›Full record

ArticleGenes and immunity

Genetic analysis of the pathogenic molecular sub-phenotype interferon-alpha identifies multiple novel loci involved in systemic lupus erythematosus.

S N Kariuki, Y Ghodke-Puranik, J M Dorschner, B S Chrabot, J A Kelly, B P Tsao, R P Kimberly, M E Alarcón-Riquelme, C O Jacob, L A Criswell and 5 more

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

Article in Genes and immunity. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed, 1 pooled it
2.5field-weighted citation impact, top 10% 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

46 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.

  1. Pooled it
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  6. Article
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  11. Article
  12. Gain-of-functionClinical kidney journal · 2022
    Article
  13. Evolutionary Origins of Metabolic Reprogramming in Cancer.International journal of molecular sciences · 2022
    Review
  14. Interferon pathway lupus risk alleles modulate risk of death from acute COVID-19.Translational research : the journal of laboratory and clinical medicine · 2022
    Article
  15. BackboneBiomolecular NMR assignments · 2022
    Article
  16. Type I Interferons in Autoimmunity.The Journal of investigative dermatology · 2022
    Review
  17. Interferon pathway lupus risk alleles modulate risk of death from acute COVID-19.medRxiv : the preprint server for health sciences · 2021
    Article
  18. Article
  19. Review
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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

15 authors at 9 institutions in 2 countries.

S N KariukiDepartment of Human Genetics, University of Chicago, Chicago, IL, USA.
Y Ghodke-PuranikDepartment of Immunology and Division of Rheumatology, Mayo Clinic, Rochester, MN, USA.ORCID 0000000162320550
J M DorschnerDepartment of Immunology and Division of Rheumatology, Mayo Clinic, Rochester, MN, USA.
B S ChrabotGwen Knapp Center for Lupus Research, University of Chicago, Chicago, IL, USA.
J A KellyArthritis & Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
B P TsaoDepartment of Medicine, University of California, Los Angeles, CA, USA.
R P KimberlyDepartment of Medicine, University of Alabama, Birmingham, AL, USA.
M E Alarcón-Riquelme1] Arthritis & Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA [2] GENYO Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, Granada, Spain.
C O JacobDepartment of Medicine, University of Southern California, Los Angeles, CA, USA.
L A CriswellRosalind Russell/Ephraim P Engleman Rheumatology Research Center, University of California, San Francisco, CA, USA.
K L SivilsArthritis & Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
C D LangefeldDepartment of Biostatistical Sciences, Wake Forest University, Winston-Salem, NC, USA.
J B HarleyCincinnati Children's Hospital Medical Center and Cincinnati VA Medical Center, Cincinnati, OH, USA.
A D SkolDepartment of Human Genetics, University of Chicago, Chicago, IL, USA.
T B NiewoldDepartment of Immunology and Division of Rheumatology, Mayo Clinic, Rochester, MN, USA.
Mayo Clinic in Arizona · USOklahoma Medical Research Foundation · USUniversity of Chicago · USCincinnati Children's Hospital Medical Center · USUniversity of Alabama at Birmingham · USUniversity of California, Los Angeles · USUniversity of California, San Francisco · USUniversity of Southern California · USWake Forest University · US

Funding

Engaging University of California Stakeholders for Biorespository ResearchUL1TR000004 · NCATS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GRANDIS, JENNIFER RUBIN · 2012 to 2015
$78.0M
TRANSLATIONAL RESEARCH UNIVERSITY OF CHICAGO: CLINICAL TRIALSUL1RR024999 · NCRR · UNIVERSITY OF CHICAGO · PI SOLWAY, JULIAN · 2007 to 2011
$25.3M
VALIDATING NOVEL GENES IMPLICATED IN LEUKOCYTE CHEMOTAXISP20RR020143 · NCRR · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI GAFFNEY, PATRICK M · 2004 to 2011
$21.0M
The Interplay of Sociodemographic and Genetic Factors in SLE Health DisparitiesP60AR053308 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KATZ, PATRICIA P · 2006 to 2016
$11.8M
SequencingP01AI083194 · NIAID · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI KIMBERLY, ROBERT P. · 2009 to 2013
$9.6M
GENE MAPPING IN WOMEN WITH SYSTEMIC LUPUS ERYTHEMATOSUSR01AR043274 · NIAMS · UNIVERSITY OF MINNESOTA TWIN CITIES · PI SIVILS, KATHY L. · 1996 to 2010
$6.5M
CHROMOSOME REGIONS LINKED TO SLE IN MULTIPLEX FAMILIESR01AR043814 · NIAMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TSAO, BETTY P · 1997 to 2012
$5.7M
GENETIC ASSOCIATION WITH LUPUS IN AMERICAN BLACKSR01AR042460 · NIAMS · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI HARLEY, JOHN BARKER · 1993 to 2009
$5.1M
LUPUS FAMILY REGISTRY AND REPOSITORYN01AR62277 · NIAMS · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI HARLEY, JOHN · 2007 to 2009
$4.0M
Interferon Alpha as a Tool for Gene Discovery in Human LupusR01AR060861 · NIAMS · UNIVERSITY OF CHICAGO · PI NIEWOLD, TIMOTHY B · 2011 to 2015
$1.8M
Identification of Susceptibility Genes for SLE of Amerindian Origin in HispanicsRC1AR058621 · NIAMS · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI ALARCON-RIQUELME, MARTA E · 2009 to 2010
$1.0M
Genetic Regulation of interferon Alpha in Human LupusK08AI083790 · NIAID · UNIVERSITY OF CHICAGO · PI NIEWOLD, TIMOTHY B · 2009 to 2013
$616k
BLRD VA I01 BX001834Howard Hughes Medical InstituteNCATS NIH HHS UL1 TR000004NCI NIH HHS R01 CA141700NCRR NIH HHS P20 RR020143NCRR NIH HHS UL1 RR024999NIAID NIH HHS AI071651NIAID NIH HHS K08 AI083790NIAID NIH HHS L30 AI071651NIAID NIH HHS P01 AI083194NIAMS NIH HHS AR042460NIAMS NIH HHS AR053308NIAMS NIH HHS N01 AR062277NIAMS NIH HHS N01 AR62277NIAMS NIH HHS P60 AR053308NIAMS NIH HHS R01 AR042460NIAMS NIH HHS R01 AR043274NIAMS NIH HHS R01 AR043814NIAMS NIH HHS R01 AR060861NIAMS NIH HHS R01 AR43814NIAMS NIH HHS RC1 AR058621NIDCR NIH HHS R01 DE018209
6 · The paper itself

Abstract

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by inflammation of multiple organ systems and dysregulated interferon responses. SLE is both genetically and phenotypically heterogeneous, greatly reducing the power of case-control studies in SLE. Elevated circulating interferon-alpha (IFN-α) is a stable, heritable trait in SLE, which has been implicated in primary disease pathogenesis. About 40-50% of patients have high IFN-α, and high levels correspond with clinical differences. To study genetic heterogeneity in SLE, we performed a case-case study comparing patients with high vs low IFN-α in over 1550 SLE cases, including genome-wide association study and replication cohorts. In meta-analysis, the top associations in European ancestry were protein kinase, cyclic GMP-dependent, type I (PRKG1) rs7897633 (P(Meta) = 2.75 × 10(-8)) and purine nucleoside phosphorylase (PNP) rs1049564 (P(Meta) = 1.24 × 10(-7)). We also found evidence for cross-ancestral background associations with the ankyrin repeat domain 44 (ANKRD44) and pleckstrin homology domain containing, family F member 2 gene (PLEKHF2) loci. These loci have not been previously identified in case-control SLE genetic studies. Bioinformatic analyses implicated these loci functionally in dendritic cells and natural killer cells, both of which are involved in IFN-α production in SLE. As case-control studies of heterogeneous diseases reach a limit of feasibility with respect to subject number and detectable effect size, the study of informative pathogenic sub-phenotypes becomes an attractive strategy for genetic discovery in complex disease.

Indexed as

Polymorphism, Single NucleotideCase-Control StudiesCyclic GMP-Dependent Protein Kinase Type IFemaleGene Regulatory NetworksHumansInterferon-alphaLupus Erythematosus, SystemicPurine-Nucleoside PhosphorylaseWhite PeopleCyclic GMP-Dependent Protein Kinase Type IInterferon-alphaPRKG1 protein, humanPurine-Nucleoside Phosphorylase

Identifiers

PMID25338677
PMCPMC4305028
OpenAlexW2076831973

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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.