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Dense genotyping of immune-related loci identifies HLA variants associated with increased risk of collagenous colitis

Overview of attention for article published in Gut, November 2015
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Title
Dense genotyping of immune-related loci identifies HLA variants associated with increased risk of collagenous colitis
Published in
Gut, November 2015
DOI 10.1136/gutjnl-2015-309934
Pubmed ID
Authors

Helga Westerlind, Marie-Rose Mellander, Francesca Bresso, Andreas Munch, Ferdinando Bonfiglio, Ghazaleh Assadi, Joseph Rafter, Matthias Hübenthal, Wolfgang Lieb, Henrik Källberg, Boel Brynedal, Leonid Padyukov, Jonas Halfvarson, Leif Törkvist, Jan Bjork, Anna Andreasson, Lars Agreus, Sven Almer, Stephan Miehlke, Ahmed Madisch, Bodil Ohlsson, Robert Löfberg, Rolf Hultcrantz, Andre Franke, Mauro D'Amato

Abstract

Collagenous colitis (CC) is a major cause of chronic non-bloody diarrhoea, particularly in the elderly female population. The aetiology of CC is unknown, and still poor is the understanding of its pathogenesis. This possibly involves dysregulated inflammation and immune-mediated reactions in genetically predisposed individuals, but the contribution of genetic factors to CC is underinvestigated. We systematically tested immune-related genes known to impact the risk of several autoimmune diseases for their potential CC-predisposing role. Three independent cohorts of histologically confirmed CC cases (N=314) and controls (N=4299) from Sweden and Germany were included in a 2-step association analysis. Immunochip and targeted single nucleotide polymorphism (SNP) genotype data were produced, respectively, for discovery and replication purposes. Classical human leucocyte antigen (HLA) variants at 2-digit and 4-digit resolution were obtained via imputation from single marker genotypes. SNPs and HLA variants passing quality control filters were tested for association with CC with logistic regression adjusting for age, sex and country of origin. Forty-two markers gave rise to genome-wide significant association signals, all contained within the HLA region on chromosome 6 (best p=4.2×10(-10) for SNP rs4143332). Among the HLA variants, most pronounced risk effects were observed for 8.1 haplotype alleles including DQ2.5, which was targeted and confirmed in the replication data set (p=2.3×10(-11); OR=2.06; 95% CI (1.67 to 2.55) in the combined analysis). HLA genotype associates with CC, thus implicating HLA-related immune mechanisms in its pathogenesis.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 44 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Spain 2 5%
Germany 1 2%
Unknown 41 93%

Demographic breakdown

Readers by professional status Count As %
Researcher 10 23%
Other 7 16%
Student > Ph. D. Student 4 9%
Professor 3 7%
Student > Doctoral Student 3 7%
Other 10 23%
Unknown 7 16%
Readers by discipline Count As %
Medicine and Dentistry 16 36%
Agricultural and Biological Sciences 7 16%
Biochemistry, Genetics and Molecular Biology 5 11%
Nursing and Health Professions 1 2%
Psychology 1 2%
Other 1 2%
Unknown 13 30%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 12 November 2015.
All research outputs
#14,827,682
of 22,831,537 outputs
Outputs from Gut
#5,533
of 6,833 outputs
Outputs of similar age
#157,649
of 285,068 outputs
Outputs of similar age from Gut
#46
of 55 outputs
Altmetric has tracked 22,831,537 research outputs across all sources so far. This one is in the 32nd percentile – i.e., 32% of other outputs scored the same or lower than it.
So far Altmetric has tracked 6,833 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 18.3. This one is in the 17th percentile – i.e., 17% of its peers scored the same or lower than it.
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 285,068 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 41st percentile – i.e., 41% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 55 others from the same source and published within six weeks on either side of this one. This one is in the 14th percentile – i.e., 14% of its contemporaries scored the same or lower than it.