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Cross-phenotype association mapping of the MHC identifies genetic variants that differentiate psoriatic arthritis from psoriasis

Overview of attention for article published in Annals of the Rheumatic Diseases, August 2017
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (80th percentile)
  • Average Attention Score compared to outputs of the same age and source

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Title
Cross-phenotype association mapping of the MHC identifies genetic variants that differentiate psoriatic arthritis from psoriasis
Published in
Annals of the Rheumatic Diseases, August 2017
DOI 10.1136/annrheumdis-2017-211414
Pubmed ID
Authors

John Bowes, James Ashcroft, Nick Dand, Farideh Jalali-najafabadi, Eftychia Bellou, Pauline Ho, Helena Marzo-Ortega, Philip S Helliwell, Marie Feletar, Anthony W Ryan, David J Kane, Eleanor Korendowych, Michael A Simpson, Jonathan Packham, Ross McManus, Matthew A Brown, Catherine H Smith, Jonathan N Barker, Neil McHugh, Oliver FitzGerald, Richard B Warren, Anne Barton

Abstract

Psoriatic arthritis (PsA) is a chronic inflammatory arthritis, with a strong heritable component, affecting patients with psoriasis. Here we attempt to identify genetic variants within the major histocompatibility complex (MHC) that differentiate patients with PsA from patients with cutaneous psoriasis alone (PsC). 2808 patients with PsC, 1945 patients with PsA and 8920 population controls were genotyped. We imputed SNPs, amino acids and classical HLA alleles across the MHC and tested for association with PsA compared to population controls and the PsC patient group. In addition we investigated the impact of the age of disease onset on associations. HLA-C*06:02 was protective of PsA compared to PsC (p=9.57x10-66, OR 0.37). The HLA-C*06:02 risk allele was associated with a younger age of psoriasis onset in all patients (p=1.01x10-59). After controlling for the age of psoriasis onset no association of PsA to HLA-C*06:02 (p=0.07) was observed; instead, the most significant association was to amino acid at position 97 of HLA-B (p=1.54x10-9) where the presence of asparagine or serine residue increased PsA risk. Asparagine at position 97 of HLA-B defines the HLA-B*27 alleles. By controlling for the age of psoriasis onset, we show, for the first time, that HLA-C*06:02 is not associated with PsA and that amino acid position 97 of HLA-B differentiates PsA from PsC. This amino acid also represents the largest genetic effect for ankylosing spondylitis, thereby refining the genetic overlap of these two spondyloarthropathies. Correcting for bias has important implications for cross-phenotype genetic studies.

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X Demographics

The data shown below were collected from the profiles of 13 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 84 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 84 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 12 14%
Other 11 13%
Researcher 10 12%
Student > Bachelor 10 12%
Student > Master 10 12%
Other 13 15%
Unknown 18 21%
Readers by discipline Count As %
Medicine and Dentistry 31 37%
Biochemistry, Genetics and Molecular Biology 12 14%
Agricultural and Biological Sciences 8 10%
Immunology and Microbiology 7 8%
Neuroscience 3 4%
Other 6 7%
Unknown 17 20%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 10. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 01 July 2018.
All research outputs
#3,584,832
of 24,892,887 outputs
Outputs from Annals of the Rheumatic Diseases
#2,131
of 7,725 outputs
Outputs of similar age
#62,749
of 324,204 outputs
Outputs of similar age from Annals of the Rheumatic Diseases
#49
of 85 outputs
Altmetric has tracked 24,892,887 research outputs across all sources so far. Compared to these this one has done well and is in the 85th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 7,725 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 14.1. This one has gotten more attention than average, scoring higher than 72% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 324,204 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 80% of its contemporaries.
We're also able to compare this research output to 85 others from the same source and published within six weeks on either side of this one. This one is in the 43rd percentile – i.e., 43% of its contemporaries scored the same or lower than it.