Evidence map›Paper›PMID 22174698›Full record

SynthesisPLoS genetics2011

A comprehensive analysis of shared loci between systemic lupus erythematosus (SLE) and sixteen autoimmune diseases reveals limited genetic overlap.

Paula S Ramos, Lindsey A Criswell, Kathy L Moser, Mary E Comeau, Adrienne H Williams, Nicholas M Pajewski, Sharon A Chung, Robert R Graham, Raphael Zidovetzki, Jennifer A Kelly and 10 more

Open access · goldAbstract readMeta-Analysis
In one paragraph

Synthesis in PLoS genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
114citing papers in PubMed, 7 pooled it
12.0field-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

114 citing papers in PubMed, 7 syntheses or guidelines pooled it, 173 citations in OpenAlex.

  1. Pooled it
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  14. Sequential immunotherapy: towards cures for autoimmunity.Nature reviews. Drug discovery · 2024
    Review
  15. Article
  16. Article
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  18. Article
  19. Association betweenMedicina (Kaunas, Lithuania) · 2023
    Article
  20. Article

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

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

20 authors at 11 institutions in 3 countries.

Paula S RamosDepartment of Medicine, Medical University of South Carolina, Charleston, South Carolina, United States of America. ramosp@musc.edu
Lindsey A Criswell
Kathy L Moser
Mary E Comeau
Adrienne H Williams
Nicholas M Pajewski
Sharon A Chung
Robert R Graham
Raphael Zidovetzki
Jennifer A Kelly
Kenneth M Kaufman
Chaim O Jacob
Timothy J Vyse
Betty P Tsao
Robert P Kimberly
Patrick M Gaffney
Marta E Alarcón-Riquelme
John B Harley
Carl D Langefeld
International Consortium on the Genetics of Systemic Erythematosus
Wake Forest University · USOklahoma Medical Research Foundation · USCincinnati Children's Hospital Medical Center · USUniversity of California, San Francisco · USKing's College London · GBMedical University of South Carolina · USPfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research · ESUniversity of Alabama at Birmingham · USUniversity of California, Los Angeles · USUniversity of California, Riverside · USUniversity of Southern California · US

Funding

ZD1839 FOR MALIGNANT ASTROCYTOMA OR GLIOBLASTOMA AND MENINGIOMAM01RR000079 · NCRR · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KESSLER, DAVID A · 1985 to 2006
$26.0M
VALIDATING NOVEL GENES IMPLICATED IN LEUKOCYTE CHEMOTAXISP20RR020143 · NCRR · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI ALARCON-RIQUELME, MARTA E · 2004 to 2011
$21.0M
CTSA: K12 COMPONENTKL2RR024130 · NCRR · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JOHNSTON, S. CLAIBORNE · 2006 to 2011
$19.3M
Program Project in the Genetics of SLEP01AR049084 · NIAMS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI KIMBERLY, ROBERT P. · 2002 to 2012
$12.7M
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
HLA GENE COMPLEMENTATION IN PRIMARY SJOGREN'S AND LUPUSR01AI024717 · NIAID · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI KOTTYAN, LEAH CLAIRE, WEIRAUCH, MATTHEW TYSON · 1987 to 2025
$7.8M
SNP Confirmation and High Throughput Genotyping CoreP30AR053483 · NIAMS · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI GUTHRIDGE, JOEL MARVIN · 2007 to 2017
$6.7M
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
Genetic Linkage in LupusR37AI024717 · NIAID · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI HARLEY, JOHN BARKER · 2005 to 2014
$4.2M
MONONUCLEAR PHAGOCYTE FUNCTION IN IMMUNOLOGIC DISEASESR01AR033062 · NIAMS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI KIMBERLY, ROBERT P. · 1986 to 2010
$3.8M
Comprehensive Candidate Pathway Analysis in SLER01AI063274 · NIAID · UNIVERSITY OF MINNESOTA TWIN CITIES · PI GAFFNEY, PATRICK M · 2005 to 2009
$3.1M
NCRR NIH HHS KL2 RR024130NCRR NIH HHS M01 RR-000079NCRR NIH HHS M01 RR000079NCRR NIH HHS P20 RR020143NCRR NIH HHS RR020143NCRR NIH HHS RR024130NIAID NIH HHS AI024717NIAID NIH HHS AI063274NIAID NIH HHS R01 AI024717NIAID NIH HHS R01 AI063274NIAID NIH HHS R37 AI024717NIAID NIH HHS R56 AI063274NIAMS NIH HHS AR02175NIAMS NIH HHS AR042460NIAMS NIH HHS AR043247NIAMS NIH HHS AR043814NIAMS NIH HHS AR044804NIAMS NIH HHS AR049084NIAMS NIH HHS AR053308NIAMS NIH HHS AR33062NIAMS NIH HHS AR445650NIAMS NIH HHS AR49084NIAMS NIH HHS K24 AR002175NIAMS NIH HHS N01 AR062277NIAMS NIH HHS P01 AR049084NIAMS NIH HHS P30 AR053483NIAMS NIH HHS P60 AR053308NIAMS NIH HHS R01 AR033062NIAMS NIH HHS R01 AR042460NIAMS NIH HHS R01 AR043814Wellcome TrustWellcome Trust 085492
6 · The paper itself

Abstract

In spite of the well-known clustering of multiple autoimmune disorders in families, analyses of specific shared genes and polymorphisms between systemic lupus erythematosus (SLE) and other autoimmune diseases (ADs) have been limited. Therefore, we comprehensively tested autoimmune variants for association with SLE, aiming to identify pleiotropic genetic associations between these diseases. We compiled a list of 446 non-Major Histocompatibility Complex (MHC) variants identified in genome-wide association studies (GWAS) of populations of European ancestry across 17 ADs. We then tested these variants in our combined Caucasian SLE cohorts of 1,500 cases and 5,706 controls. We tested a subset of these polymorphisms in an independent Caucasian replication cohort of 2,085 SLE cases and 2,854 controls, allowing the computation of a meta-analysis between all cohorts. We have uncovered novel shared SLE loci that passed multiple comparisons adjustment, including the VTCN1 (rs12046117, P = 2.02×10(-06)) region. We observed that the loci shared among the most ADs include IL23R, OLIG3/TNFAIP3, and IL2RA. Given the lack of a universal autoimmune risk locus outside of the MHC and variable specificities for different diseases, our data suggests partial pleiotropy among ADs. Hierarchical clustering of ADs suggested that the most genetically related ADs appear to be type 1 diabetes with rheumatoid arthritis and Crohn's disease with ulcerative colitis. These findings support a relatively distinct genetic susceptibility for SLE. For many of the shared GWAS autoimmune loci, we found no evidence for association with SLE, including IL23R. Also, several established SLE loci are apparently not associated with other ADs, including the ITGAM-ITGAX and TNFSF4 regions. This study represents the most comprehensive evaluation of shared autoimmune loci to date, supports a relatively distinct non-MHC genetic susceptibility for SLE, provides further evidence for previously and newly identified shared genes in SLE, and highlights the value of studies of potentially pleiotropic genes in autoimmune diseases.

Indexed as

Arthritis, RheumatoidAutoimmune DiseasesCase-Control StudiesCohort StudiesColitis, UlcerativeCrohn DiseaseDiabetes Mellitus, Type 1Genetic PleiotropyGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansInterleukin-2 Receptor alpha SubunitLupus Erythematosus, SystemicOX40 LigandPolymorphism, Single NucleotideReceptors, InterleukinIL23R protein, humanIL2RA protein, humanInterleukin-2 Receptor alpha SubunitOX40 LigandReceptors, InterleukinTNFSF4 protein, humanV-Set Domain-Containing T-Cell Activation Inhibitor 1VTCN1 protein, human

Identifiers

PMID22174698
PMCPMC3234215
OpenAlexW1972985967

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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.