Evidence map›Paper›PMID 25087609›Full record

ArticleAmerican journal of human genetics2014

Fine mapping major histocompatibility complex associations in psoriasis and its clinical subtypes.

Yukinori Okada, Buhm Han, Lam C Tsoi, Philip E Stuart, Eva Ellinghaus, Trilokraj Tejasvi, Vinod Chandran, Fawnda Pellett, Remy Pollock, Anne M Bowcock and 12 more

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

Article in American journal of human genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
101citing papers in PubMed, 7 pooled it
9.3field-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

101 citing papers in PubMed, 7 syntheses or guidelines pooled it, 218 citations in OpenAlex.

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  8. Polygenic risk for skin autoimmunity impacts immune checkpoint blockade in bladder cancer.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Trial
  9. Trial
  10. Review
  11. Article
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  14. Global epidemiology of spondyloarthritis.Nature reviews. Rheumatology · 2025
    Review
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  16. Review
  17. Article
  18. Exploration of the causality of frailty index on psoriasis: A Mendelian randomization study.Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging (ISSI) · 2024
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41 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

22 authors at 12 institutions in 6 countries.

Yukinori OkadaDepartment of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-0085, Japan; Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan; Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Division of Genetics, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA 02142, USA.
Buhm HanDivision of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Division of Genetics, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA 02142, USA.
Lam C TsoiDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
Philip E StuartDepartment of Dermatology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Eva EllinghausInstitute of Clinical Molecular Biology, Kiel University, Kiel 24105, Germany.
Trilokraj TejasviDepartment of Dermatology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Vinod ChandranDivision of Rheumatology, Department of Medicine, University of Toronto, Toronto, ON M5T 2S8, Canada; Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Research Institute, University of Toronto, Toronto, ON M5T 2S8, Canada.
Fawnda PellettCentre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Research Institute, University of Toronto, Toronto, ON M5T 2S8, Canada.
Remy PollockCentre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Research Institute, University of Toronto, Toronto, ON M5T 2S8, Canada.
Anne M BowcockNational Heart and Lung Institute, Imperial College, London SW7 2AZ, UK.
Gerald G KruegerDepartment of Dermatology, University of Utah, Salt Lake City, UT 84112, USA.
Michael WeichenthalDepartment of Dermatology, Christian-Albrechts-Universität zu Kiel, Kiel 24105, Germany.
John J VoorheesDepartment of Dermatology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Proton RahmanMemorial University of Newfoundland, St. John's, NL A1C5S7, Canada.
Peter K GregersenThe Feinstein Institute for Medical Research, North Shore - Long Island Jewish Health System, Manhasset, NY 11030, USA.
Andre FrankeInstitute of Clinical Molecular Biology, Kiel University, Kiel 24105, Germany.
Rajan P NairDepartment of Dermatology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Gonçalo R AbecasisDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
Dafna D GladmanDivision of Rheumatology, Department of Medicine, University of Toronto, Toronto, ON M5T 2S8, Canada; Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Research Institute, University of Toronto, Toronto, ON M5T 2S8, Canada; Toronto Western Research Institute, University of Toronto, Toronto, ON M5G 2M9, Canada.
James T ElderDepartment of Dermatology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Ann Arbor Veterans Affairs Hospital, Ann Arbor, MI 48105, USA.
Paul I W de BakkerDepartment of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht 3584 CG, the Netherlands; Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht 3584 CG, the Netherlands. Electronic address: pdebakker@umcutrecht.nl.
Soumya RaychaudhuriDivision of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Division of Genetics, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA 02142, USA; Arthritis Research UK Epidemiology Unit, Centre for Musculoskeletal Research, Institute of Inflammation and Repair, University of Manchester, Manchester M13 9PT, UK. Electronic address: soumya@broadinstitute.org.
University of Michigan–Ann Arbor · USKiel University · DEToronto Western Hospital · CABroad Institute · USHarvard University · USImperial College London · GBMemorial University of Newfoundland · CANorthwell Health · USRIKEN Center for Integrative Medical Sciences · JPUniversity Medical Center Utrecht · NLUniversity of Toronto · CAUniversity of Utah · US

Funding

Linkage analysis of familial psoriasis(Supplement)R01AR042742 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ELDER, JAMES TILFORD · 1994 to 2021
$10.1M
Genetic predictors of response to anti-TNF therapy in rheumatoid arthritisU01GM092691 · NIGMS · BRIGHAM AND WOMEN'S HOSPITAL · PI BRENNER, MICHAEL B., RAYCHAUDHURI, SOUMYA · 2010 to 2014
$7.5M
Genetic and Genomic Dissection of Psoriatic ArthritisR01AR063611 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ELDER, JAMES TILFORD, GLADMAN, DAFNA D · 2012 to 2023
$6.2M
Genome-Wide SNP Association in PsoriasisR01AR050266 · NIAMS · WASHINGTON UNIVERSITY · PI BOWCOCK, ANNE MARY · 2007 to 2016
$5.7M
Discovery and Functional Impact of Common and Rare Variants in RAR01AR063759 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI Soumya Raychaudhuri · 2013 to 2026
$5.4M
Identification of Psoriatic Arthritis Genes in the MHCR01AR050511 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ELDER, JAMES TILFORD · 2004 to 2013
$4.2M
Functional Genomics of PsoriasisR01AR065183 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ELDER, JAMES TILFORD · 2013 to 2016
$1.7M
Fine-mapping the MHC associations in rheumatoid arthritis from GWAS dataR01AR062886 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI RAYCHAUDHURI, SOUMYA · 2012 to 2013
$783k
CIHRNIAMS NIH HHS 1R01AR062886NIAMS NIH HHS 1R01AR063759-01A1NIAMS NIH HHS 2R01AR050266NIAMS NIH HHS R01 AR042742NIAMS NIH HHS R01AR042742NIAMS NIH HHS R01 AR050266NIAMS NIH HHS R01 AR050511NIAMS NIH HHS R01AR050511NIAMS NIH HHS R01AR062382NIAMS NIH HHS R01 AR062886NIAMS NIH HHS R01 AR063611NIAMS NIH HHS R01 AR063759NIAMS NIH HHS R01 AR065183NIGMS NIH HHS 5U01GM092691-04NIGMS NIH HHS U01 GM092691
6 · The paper itself

Abstract

Psoriasis vulgaris (PsV) risk is strongly associated with variation within the major histocompatibility complex (MHC) region, but its genetic architecture has yet to be fully elucidated. Here, we conducted a large-scale fine-mapping study of PsV risk in the MHC region in 9,247 PsV-affected individuals and 13,589 controls of European descent by imputing class I and II human leukocyte antigen (HLA) genes from SNP genotype data. In addition, we imputed sequence variants for MICA, an MHC HLA-like gene that has been associated with PsV, to evaluate association at that locus as well. We observed that HLA-C(∗)06:02 demonstrated the lowest p value for overall PsV risk (p = 1.7 × 10(-364)). Stepwise analysis revealed multiple HLA-C(∗)06:02-independent risk variants in both class I and class II HLA genes for PsV susceptibility (HLA-C(∗)12:03, HLA-B amino acid positions 67 and 9, HLA-A amino acid position 95, and HLA-DQα1 amino acid position 53; p < 5.0 × 10(-8)), but no apparent risk conferred by MICA. We further evaluated risk of two major clinical subtypes of PsV, psoriatic arthritis (PsA; n = 3,038) and cutaneous psoriasis (PsC; n = 3,098). We found that risk heterogeneity between PsA and PsC might be driven by HLA-B amino acid position 45 (Pomnibus = 2.2 × 10(-11)), indicating that different genetic factors underlie the overall risk of PsV and the risk of specific PsV subphenotypes. Our study illustrates the value of high-resolution HLA and MICA imputation for fine mapping causal variants in the MHC.

Indexed as

Amino Acid SequenceArthritis, PsoriaticBase SequenceChromosome MappingGenetic Association StudiesGenetic Predisposition to DiseaseGenotypeHistocompatibility Antigens Class IHistocompatibility Antigens Class IIHLA-B AntigensHLA-C AntigensHumansMajor Histocompatibility ComplexPolymorphism, Single NucleotidePsoriasisHistocompatibility Antigens Class IHistocompatibility Antigens Class IIHLA-B AntigensHLA-C*06:02 antigenHLA-C AntigensMHC class I-related chain A

Identifiers

PMID25087609
PMCPMC4129407
OpenAlexW2152633345

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LicenceCC BY
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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.