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Dense genotyping of...
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Westerlind, HelgaKarolinska Institutet,Karolinska Institute,Karolinska Institutet, Stockholm, Sweden
(author)
Dense genotyping of immune-related loci identifies HLA variants associated with increased risk of collagenous colitis.
- Article/chapterEnglish2017
Publisher, publication year, extent ...
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2015-11-02
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BMJ Publishing Group Ltd,2017
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:liu-125456
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https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-125456URI
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https://doi.org/10.1136/gutjnl-2015-309934DOI
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https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-56833URI
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https://lup.lub.lu.se/record/8243588URI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:135205148URI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Funding agencies: Swedish Research Council [VR 2010-2976, VR 2013-3862]; Swedish Society of Medicine; Research Council of South-East Sweden (FORSS); County Council of Ostergotland (ALF); Bengt Ihres fond; Bengt Ihre Research Fellowship; Magtarmfonden; Stockholm County Coun
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Funding Agencies:Research Council of South-East Sweden (FORSS)County Council of Östergötland (ALF)Bengt Ihre's fondBengt Ihre Research FellowshipMagtarmfondenStockholm County Council 530084German Ministry of Education and Research (BMBF) through the e:Med consortium sysINFLAMEGerman Ministry for Education and Research 01EY1103European Union 262055
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OBJECTIVE: 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.DESIGN: 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.RESULTS: 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).CONCLUSIONS: HLA genotype associates with CC, thus implicating HLA-related immune mechanisms in its pathogenesis.
Subject headings and genre
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Mellander, Marie-RoseKarolinska Institute,Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
(author)
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Bresso, FrancescaKarolinska Institute,Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
(author)
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Munch, AndreasLinköping University,Linköpings universitet,Avdelningen för neuro- och inflammationsvetenskap,Hälsouniversitetet,Dept Clin & Expt Med, Fac Hlth Sci, Linköpings Univ, Linköping, Sweden(Swepub:liu)andsa76
(author)
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Bonfiglio, FerdinandoKarolinska Institutet,Karolinska Institute,Karolinska Institutet, Stockholm, Sweden
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Assadi, GhazalehKarolinska Institutet,Karolinska Institute,Karolinska Institutet, Stockholm, Sweden
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Rafter, JosephKarolinska Institutet,Karolinska Institute,Karolinska Institutet, Stockholm, Sweden
(author)
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Hübenthal, MatthiasChristian-Albrechts-University of Kiel, Kiel, Germany,Inst Clin Mol Biol, Christian Albrechts Univ Kiel, Kiel, Germany
(author)
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Lieb, WolfgangChristian-Albrechts-University of Kiel, Kiel, Germany,Inst Epidemiol, Christian Albrechts Univ Kiel, Kiel, Germany; Biobank POPGEN, Christian Albrechts Univ Kiel, Kiel, Germany
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Källberg, HenrikKarolinska Institute,Karolinska Institutet, Stockholm, Sweden
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Brynedal, BoelKarolinska Institutet,Karolinska Institute,Karolinska Institutet, Stockholm, Sweden
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Padyukov, LeonidKarolinska Institutet,Karolinska Institute,Karolinska Institutet, Stockholm, Sweden
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Halfvarson, Jonas,1970-Örebro University,Örebro universitet,Institutionen för medicinska vetenskaper,Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden,Faculty of Medicine and Health, Örebro University, Örebro, Sweden(Swepub:oru)jshn
(author)
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Törkvist, LeifKarolinska Institutet,Karolinska University Hospital, Stockholm, Sweden
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Bjork, JanKarolinska University Hospital, Stockholm, Sweden,Gastroctr, Karolinska Univ Hosp, Stockholm, Sweden
(author)
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Andreasson, AnnaKarolinska Institutet,Karolinska Institute,Karolinska Institutet, Stockholm, Sweden
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Agreus, LarsKarolinska Institutet,Karolinska Institute,Karolinska Institutet, Stockholm, Sweden
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Almer, SvenKarolinska Institutet,Karolinska Institute,arolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
(author)
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Miehlke, StephanInternal Medicine Center Eppendorf, Hamburg, Germany,Ctr Digest Dis, Internal Med Ctr Eppendorf, Hamburg, Germany,University Medical Center Hamburg-Eppendorf
(author)
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Madisch, AhmedSiloah Hospital, Hannover, Germany,Clin Gastroenterol Endoscopy & Intervent Diabetol, Siloah Hosp, Hannover, Germany
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Ohlsson, BodilLund University,Lunds universitet,Internmedicin - epidemiologi,Forskargrupper vid Lunds universitet,Internal Medicine - Epidemiology,Lund University Research Groups,Skåne University Hospital, Lund University, Lund, Sweden(Swepub:lu)kir-boh
(author)
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Löfberg, RobertKarolinska Institute,Karolinska Institutet, Stockholm, Sweden Sophiahemmet Hospital, Stockholm, Sweden
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Hultcrantz, RolfKarolinska Institutet,Karolinska Institute,Karolinska Institutet, Stockholm, Sweden
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Franke, AndreChristian-Albrechts-University of Kiel, Kiel, Germany,Inst Clin Mol Biol, Christian Albrechts Univ Kiel, Kiel, Germany
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D'Amato, MauroKarolinska Institute,Karolinska Institutet, Stockholm, Sweden BioCruces Health Research Institute and IKERBASQUE, Basque Foundation for Science, Bilbao, Spain.
(author)
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Karolinska InstitutetKarolinska Institute
(creator_code:org_t)
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In:Gut: BMJ Publishing Group Ltd66:3, s. 421-4280017-57491468-3288
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Munch, Andreas
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Assadi, Ghazaleh
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Rafter, Joseph
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Lieb, Wolfgang
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Källberg, Henrik
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Brynedal, Boel
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Padyukov, Leonid
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Halfvarson, Jona ...
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Törkvist, Leif
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Bjork, Jan
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Andreasson, Anna
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Agreus, Lars
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Almer, Sven
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Miehlke, Stephan
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Madisch, Ahmed
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Ohlsson, Bodil
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Löfberg, Robert
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Hultcrantz, Rolf
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Franke, Andre
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D'Amato, Mauro
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