Evidence map›Paper›PMID 30085094›Full record

ArticleHuman molecular genetics2018

Genetic fine mapping of systemic lupus erythematosus MHC associations in Europeans and African Americans.

Ken B Hanscombe, David L Morris, Janelle A Noble, Alexander T Dilthey, Philip Tombleson, Kenneth M Kaufman, Mary Comeau, Carl D Langefeld, Marta E Alarcon-Riquelme, Patrick M Gaffney and 26 more

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

Article in Human molecular genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed, 2 pooled it
2.2field-weighted citation impact, top 12% 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

31 citing papers in PubMed, 2 syntheses or guidelines pooled it, 57 citations in OpenAlex.

  1. Pooled it
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  12. Platelet-Derived Microparticles and Autoimmune Diseases.International journal of molecular sciences · 2023
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  14. Genetic dissection ofRMD open · 2023
    Article
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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

36 authors at 14 institutions in 4 countries.

Ken B HanscombeDepartment of Medical and Molecular Genetics, King's College London, London, UK.
David L MorrisDepartment of Medical and Molecular Genetics, King's College London, London, UK.
Janelle A NobleCHORI, Children's Hospital Oakland Research Institute, Oakland, California, USA.
Alexander T DiltheyWellcome Trust Centre for Human Genetics, University of Oxford, UK.
Philip TomblesonDepartment of Medical and Molecular Genetics, King's College London, London, UK.
Kenneth M KaufmanCenter for Autoimmune Genomics and Etiology (CAGE), Department of Pediatrics, Cincinnati Children's Medical Center & University of Cincinnati and the US Department of Veterans Affairs Medical Center, Cincinnati, OH, USA.
Mary ComeauCenter for Public Health Genomics, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Carl D LangefeldCenter for Public Health Genomics, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Marta E Alarcon-RiquelmePfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research (GENYO), Granada, Spain.
Patrick M GaffneyArthritis & Clinical Immunology Research Program, Division of Genomics and Data Sciences, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
Chaim O JacobKeck School of Medicine of USC, Los Angeles, CA, USA.
Kathy L SivilsArthritis & Clinical Immunology Research Program, Division of Genomics and Data Sciences, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
Betty P TsaoDepartment of Medicine, Medical University of South Carolina, Charleston, SC, USA.
Graciela S AlarconDivision of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, USA.
Elizabeth E BrownDepartment of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.
Jennifer CrokerCenter for Clinical and Translational Science, University of Alabama at Birmingham, Birmingham, AL, USA.
Jeff EdbergDivision of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, USA.
Gary GilkesonDivision of Rheumatology, Medical University of South Carolina, Charleston, SC, USA.
Judith A JamesArthritis & Clinical Immunology Research Program, Division of Genomics and Data Sciences, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
Diane L KamenDivision of Rheumatology, Medical University of South Carolina, Charleston, SC, USA.
Jennifer A KellyArthritis & Clinical Immunology Research Program, Division of Genomics and Data Sciences, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
Joseph McCuneMichigan Medicine Rheumatology Clinic,Taubman Center Floor 3 Reception A, 1500 E Medical Center Dr SPC 5358, Ann Arbor, MI, USA.
Joan T MerrillOklahoma Medical Research Foundation,825 N.E. 13th Street, Oklahoma City, OK, USA.
Michelle PetriDivision of Rheumatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Rosalind Ramsey-GoldmanFeinberg School of Medicine,McGaw Pavilion Suite M-300, 240 E Huron, Chicago, IL, USA.
John D ReveilleDepartment of Internal Medicine, The University of Texas, Fannin, MSB, Houston, TX, USA.
Jane E SalmonDivision of Rheumatology, Hospital for Special Surgery-Weill Cornell Medicine, New York, NY, USA.
Hal ScofieldArthritis & Clinical Immunology Research Program, Division of Genomics and Data Sciences, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
Tammy UtsetUniversity of Chicago Pritzker School of Medicine, Chicago, IL, USA.
Daniel J WallaceDivision of Rheumatology, Cedars Sinai Medical Center, Los Angeles, CA, USA.
Michael H WeismanDivision of Rheumatology, Cedars Sinai Medical Center, Los Angeles, CA, USA.
Robert P KimberlyDivision of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, USA.
John B HarleyCenter for Autoimmune Genomics and Etiology (CAGE), Department of Pediatrics, Cincinnati Children's Medical Center & University of Cincinnati and the US Department of Veterans Affairs Medical Center, Cincinnati, OH, USA.
Cathryn M LewisDepartment of Medical and Molecular Genetics, King's College London, London, UK.
Lindsey A CriswellRosalind Russell / Ephraim P Engleman Rheumatology Research Center, Division of Rheumatology, UCSF School of Medicine, San Francisco, CA, USA.
Timothy J VyseDepartment of Medical and Molecular Genetics, King's College London, London, UK.
King's College London · GBOklahoma Medical Research Foundation · USUniversity of Alabama at Birmingham · USCedars-Sinai Medical Center · USMedical University of South Carolina · USChildren's Medical Center · USA. Alfred Taubman Health Care Center · USHospital for Special Surgery · USJohns Hopkins Medicine · USKeck Hospital of USC · USOaklands Hospital · GBPfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research · ESUniversity of Chicago · USUniversity of Oxford · GB

Funding

Tracking and Evaluation CoreU54GM104938 · NIGMS · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI PAUL G SPICER · 2013 to 2026
$68.2M
Northwestern University Clinical and Translational Science Institute (NUCATS)UL1TR001422 · NCATS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI D'AQUILA, RICHARD · 2015 to 2023
$56.8M
Program Project in the Genetics of SLEP01AR049084 · NIAMS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI KIMBERLY, ROBERT P. · 2002 to 2012
$12.7M
SequencingP01AI083194 · NIAID · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI KIMBERLY, ROBERT P. · 2009 to 2013
$9.6M
Oklahoma Rheumatic Disease Research Cores Center (Overall Application)P30AR073750 · NIAMS · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI JUDITH A JAMES · 2018 to 2026
$8.5M
Resource CoreP30AR072582 · NIAMS · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI JAMES C OATES · 2017 to 2026
$8.5M
RESOURCE-BASED CENTER FOR THE ADVANCEMENT OF PRECISION MEDICINE IN RHEUMATOLOGYP30AR070155 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Mary C Nakamura · 2016 to 2026
$8.2M
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
Tissue Repository CoreP30AR070549 · NIAMS · CINCINNATI CHILDRENS HOSP MED CTR · PI Leah Claire Kottyan · 2016 to 2026
$7.7M
SNP Confirmation and High Throughput Genotyping CoreP30AR053483 · NIAMS · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI GUTHRIDGE, JOEL MARVIN · 2007 to 2017
$6.7M
Pre-Clinical Studies to Identify SLE Therapeutic TargetsU19AI082714 · NIAID · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI GAFFNEY, PATRICK M · 2009 to 2018
$6.2M
Quantitative Analysis Core P30GM110766 · NIGMS · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI GAFFNEY, PATRICK M · 2014 to 2018
$6.1M
BLRD VA I01 BX001834Department of Health GUYSBRC-2007-1Department of Health MAUBRC-2012-1NCATS NIH HHS UL1 TR001422NHGRI NIH HHS U01 HG008666NIAID NIH HHS P01 AI083194NIAID NIH HHS R01 AI024717NIAID NIH HHS U01 AI101934NIAID NIH HHS U19 AI082714NIAMS NIH HHS P01 AR049084NIAMS NIH HHS P30 AR053483NIAMS NIH HHS P30 AR070155NIAMS NIH HHS P30 AR070549NIAMS NIH HHS P30 AR072582NIAMS NIH HHS P30 AR073750NIAMS NIH HHS P60 AR062755NIAMS NIH HHS P60 AR064464NIAMS NIH HHS R01 AR042460NIAMS NIH HHS R01 AR056360NIAMS NIH HHS R01 AR063124NIAMS NIH HHS R01 AR064820NIAMS NIH HHS R01 AR069572NIGMS NIH HHS P30 GM103510NIGMS NIH HHS P30 GM110766NIGMS NIH HHS U54 GM104938
6 · The paper itself

Abstract

Genetic variation within the major histocompatibility complex (MHC) contributes substantial risk for systemic lupus erythematosus, but high gene density, extreme polymorphism and extensive linkage disequilibrium (LD) have made fine mapping challenging. To address the problem, we compared two association techniques in two ancestrally diverse populations, African Americans (AAs) and Europeans (EURs). We observed a greater number of Human Leucocyte Antigen (HLA) alleles in AA consistent with the elevated level of recombination in this population. In EUR we observed 50 different A-C-B-DRB1-DQA-DQB multilocus haplotype sequences per hundred individuals; in the AA sample, these multilocus haplotypes were twice as common compared to Europeans. We also observed a strong narrow class II signal in AA as opposed to the long-range LD observed in EUR that includes class I alleles. We performed a Bayesian model choice of the classical HLA alleles and a frequentist analysis that combined both single nucleotide polymorphisms (SNPs) and classical HLA alleles. Both analyses converged on a similar subset of risk HLA alleles: in EUR HLA- B*08:01 + B*18:01 + (DRB1*15:01 frequentist only) + DQA*01:02 + DQB*02:01 + DRB3*02 and in AA HLA-C*17:01 + B*08:01 + DRB1*15:03 + (DQA*01:02 frequentist only) + DQA*02:01 + DQA*05:01+ DQA*05:05 + DQB*03:19 + DQB*02:02. We observed two additional independent SNP associations in both populations: EUR rs146903072 and rs501480; AA rs389883 and rs114118665. The DR2 serotype was best explained by DRB1*15:03 + DQA*01:02 in AA and by DRB1*15:01 + DQA*01:02 in EUR. The DR3 serotype was best explained by DQA*05:01 in AA and by DQB*02:01 in EUR. Despite some differences in underlying HLA allele risk models in EUR and AA, SNP signals across the extended MHC showed remarkable similarity and significant concordance in direction of effect for risk-associated variants.

Indexed as

Genetic Predisposition to DiseasePolymorphism, Single NucleotideBlack or African AmericanFemaleGenetic Association StudiesHaplotypesHumansLupus Erythematosus, SystemicMajor Histocompatibility ComplexMaleModels, GeneticWhite People

Identifiers

PMID30085094
PMCPMC6196648
OpenAlexW2887820187

What OpenQuestion holds

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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.