Human Leukocyte Antigen Signatures as Pathophysiological Discriminants of Microscopic Colitis Subtypes

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Human Leukocyte Antigen Signatures as Pathophysiological Discriminants of Microscopic Colitis Subtypes

Zheng, Tenghao (author): Karolinska Institute,Monash University,Monash Univ, Australia; Karolinska Inst, Sweden

Roda, Giulia (author): National Institute Of Biostructures And Biosystems,Biostruct & Biosyst Natl Inst, Italy

Zabana, Yamile (author): CIBER Enfermedades Hepaticas y Digestivas (CIBER-ehd),Mutua De Terrassa Hospital,Hosp Univ Mutua Terrassa, Spain; Ctr Invest Biomed Red Enfermedades Hepat & Digest, Spain

Escudero-Hernández, Celia (author): Linköpings universitet,Linköping University,University of Kiel,Avdelningen för molekylär medicin och virologi,Medicinska fakulteten,Univ Kiel, Germany; Univ Med Ctr Schleswig Holstein, Germany

Liu, Xingrong (author): Karolinska Institutet,Karolinska Institute,Karolinska Inst, Sweden

Chen, Ye (author): Massachusetts General Hospital,Massachusetts Gen Hosp, MA USA

Tavares, Leticia Camargo (author): Monash University,Monash Univ, Australia

Bonfiglio, Ferdinando (author): Karolinska Institute,Monash University,Monash Univ, Australia; Karolinska Inst, Sweden

Mellander, Marie Rose (author): Skåne University Hospital,Lund Univ, Sweden

Janczewska, Izabella (author): Ersta Hospital,Ersta Hosp, Sweden

Vigren, Lina (author): Lund University,Lunds universitet,Gastroenterologi,Forskargrupper vid Lunds universitet,Gastroenterology,Lund University Research Groups,Lund Univ, Sweden

Sjöberg, Klas (author): Lund University,Lunds universitet,Gastroenterologi,Forskargrupper vid Lunds universitet,LTH profilområde: Avancerade ljuskällor,LTH profilområden,Lunds Tekniska Högskola,LU profilområde: Ljus och material,Lunds universitets profilområden,Gastroenterology,Lund University Research Groups,LTH Profile Area: Photon Science and Technology,LTH Profile areas,Faculty of Engineering, LTH,LU Profile Area: Light and Materials,Lund University Profile areas,Skåne University Hospital,Lund Univ, Sweden

Ohlsson, Bodil (author): Lund University,Lunds universitet,Internmedicin - epidemiologi,Forskargrupper vid Lunds universitet,Internal Medicine - Epidemiology,Lund University Research Groups,Skåne University Hospital,Lund Univ, Sweden

Almer, Sven (author): Karolinska Institutet,Karolinska Univ Hosp, Sweden,Karolinska University Hospital

Halfvarson, Jonas (author): Örebro University Hospital,Orebro Univ Hosp, Sweden

Miehlke, Stephan (author): University Medical Center Hamburg-Eppendorf,Univ Hosp Eppendorf, Germany

Madisch, Ahmed (author): CRH Clin Siloah, Germany

Lieb, Wolfgang (author): University of Kiel,Christian Albrechts Univ Kiel, Germany

Kupčinskas, Juozas (author): Lithuanian University of Health Sciences,Lithuanian Univ Hlth Sci, Lithuania

Weersma, Rinse K. (author): University Medical Center Groningen,Univ Groningen, Netherlands; Univ Med Ctr Groningen, Netherlands

Bujanda, Luis (author): Hospital Universitario Donostia,CIBER Enfermedades Hepaticas y Digestivas (CIBER-ehd),Ctr Invest Biomed Red Enfermedades Hepat & Digest, Spain; Donostia University Hospital, Spain

Julià, Antonio (author): Vall d'Hebron University Hospital,Vall Hebron Res Inst, Spain

Marsal, Sara (author): Vall d'Hebron University Hospital,Vall Hebron Res Inst, Spain

Esteve, Maria (author): Mutua De Terrassa Hospital,CIBER Enfermedades Hepaticas y Digestivas (CIBER-ehd),Hosp Univ Mutua Terrassa, Spain; Ctr Invest Biomed Red Enfermedades Hepat & Digest, Spain

Guagnozzi, Danila (author): Vall d'Hebron University Hospital,CIBER Enfermedades Hepaticas y Digestivas (CIBER-ehd),Ctr Invest Biomed Red Enfermedades Hepat & Digest, Spain; Vall Hebron Univ Hosp, Spain

Fernández-Bañares, Fernando (author): CIBER Enfermedades Hepaticas y Digestivas (CIBER-ehd),Mutua De Terrassa Hospital,Hosp Univ Mutua Terrassa, Spain; Ctr Invest Biomed Red Enfermedades Hepat & Digest, Spain

Ferrer, Carmen (author): Mutua De Terrassa Hospital,Hosp Univ Mutua Terrassa, Spain

Peter, Inga (author): Icahn School of Medicine at Mount Sinai,Icahn Sch Med Mt Sinai, NY USA

Ludvigsson, Jonas F. (author): Karolinska Institutet,Karolinska Institute,Karolinska Inst, Sweden

Pardi, Darrell (author): Mayo Clinic Minnesota,Mayo Clin, MN USA

Verhaegh, Bas (author): Maastricht University,Maastricht Univ, Netherlands

Jonkers, Daisy (author): Maastricht University,Maastricht Univ, Netherlands

Pierik, Marieke (author): Maastricht University,Maastricht Univ, Netherlands

Münch, Andreas (author): Linköpings universitet,Linköping University,Center For Cooperative Research In Biosciences (CIC bioGUNE),Avdelningen för molekylär medicin och virologi,Institutionen för hälsa, medicin och vård,Medicinska fakulteten,Region Östergötland, Mag- tarmmedicinska kliniken

Franke, Andre (author): University of Kiel,Univ Kiel, Germany

Bresso, Francesca (author): Karolinska Institutet,Karolinska Univ Hosp, Sweden,Karolinska University Hospital

Khalili, Hamed (author): Massachusetts Institute of Technology,Massachusetts General Hospital,Massachusetts Gen Hosp, MA USA; Broad Inst Massachusetts Inst Technol & Harvard, MA USA

Colombel, Jean Frederic (author): Icahn School of Medicine at Mount Sinai,Icahn Sch Med Mt Sinai, NY USA

D’Amato, Mauro (author): Karolinska Institute,Basque Foundation for Science,Center For Cooperative Research In Biosciences (CIC bioGUNE),Karolinska Inst, Sweden; CIC bioGUNE BRTA, Spain; Basque Fdn Sci, Spain; LUM Univ, Italy

Presser, Lance (author)

Teirlinck, Anne (author)

Knol, Mirjam (author)

Piqueras, Marta (author): Consorci Sanitari de Terrassa

Busquets, David (author): Hospital Universitari de Girona Dr. Josep Trueta

Iglesias, Eva (author): Hospital Universitario Reina Sofia

Lucendo, Alfredo J. (author): CIBER Enfermedades Hepaticas y Digestivas (CIBER-ehd)

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(creator_code:org_t)

OXFORD UNIV PRESS, 2024
2024
English 11 s.
In: Journal of Crohn's and Colitis. - : OXFORD UNIV PRESS. - 1873-9946 .- 1876-4479. ; 18:3, s. 349-359

Related links:: http://dx.doi.org/10...; show more...; https://lup.lub.lu.s...; https://doi.org/10.1...; http://kipublication...; https://urn.kb.se/re...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

Background and Aims: Microscopic colitis [MC] is currently regarded as an inflammatory bowel disease that manifests as two subtypes: collagenous colitis [CC] and lymphocytic colitis [LC]. Whether these represent a clinical continuum or distinct entities is, however, an open question. Genetic investigations may contribute important insight into their respective pathophysiologies. Methods: We conducted a genome-wide association study [GWAS] meta-analysis in 1498 CC, 373 LC patients, and 13 487 controls from Europe and the USA, combined with publicly available MC GWAS data from UK Biobank and FinnGen [2599 MC cases and 552 343 controls in total]. Human leukocyte antigen [HLA] alleles and polymorphic residues were imputed and tested for association, including conditional analyses for the identification of key causative variants and residues. Genetic correlations with other traits and diagnoses were also studied. Results: We detected strong HLA association with CC, and conditional analyses highlighted the DRB1*03:01 allele and its residues Y26, N77, and R74 as key to this association (best p = 1.4 × 10-23, odds ratio [OR] = 1.96). Nominally significant genetic correlations were detected between CC and pneumonia [rg = 0.77; p = 0.048] and oesophageal diseases [rg = 0.45, p = 0.023]. An additional locus was identified in MC GWAS analyses near the CLEC16A and RMI2 genes on chromosome 16 [rs35099084, p = 2.0 × 10-8, OR = 1.31]. No significant association was detected for LC. Conclusion: Our results suggest CC and LC have distinct pathophysiological underpinnings, characterised by an HLA predisposing role only in CC. This challenges existing classifications, eventually calling for a re-evaluation of the utility of MC umbrella definitions.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Gastroenterologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Gastroenterology and Hepatology (hsv//eng)

Keyword

collagenous colitis
genetics
GWAS
HLA
Microscopic colitis
Microscopic colitis; collagenous colitis; GWAS; HLA; genetics

Publication and Content Type

art (subject category)
ref (subject category)

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By the author/editor: Zheng, Tenghao; Roda, Giulia; Zabana, Yamile; Escudero-Hernánd ...; Liu, Xingrong; Chen, Ye; show more...; Tavares, Leticia ...; Bonfiglio, Ferdi ...; Mellander, Marie ...; Janczewska, Izab ...; Vigren, Lina; Sjöberg, Klas; Ohlsson, Bodil; Almer, Sven; Halfvarson, Jona ...; Miehlke, Stephan; Madisch, Ahmed; Lieb, Wolfgang; Kupčinskas, Juoz ...; Weersma, Rinse K ...; Bujanda, Luis; Julià, Antonio; Marsal, Sara; Esteve, Maria; Guagnozzi, Danil ...; Fernández-Bañare ...; Ferrer, Carmen; Peter, Inga; Ludvigsson, Jona ...; Pardi, Darrell; Verhaegh, Bas; Jonkers, Daisy; Pierik, Marieke; Münch, Andreas; Franke, Andre; Bresso, Francesc ...; Khalili, Hamed; Colombel, Jean F ...; D’Amato, Mauro; Presser, Lance; Teirlinck, Anne; Knol, Mirjam; Piqueras, Marta; Busquets, David; Iglesias, Eva; Lucendo, Alfredo ...; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Medical Genetics

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Gastroenterology ...

Articles in the publication: Journal of Crohn ...

By the university: Lund University; Karolinska Institutet; Linköping University

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