PMID- 37768647
OWN - NLM
STAT- MEDLINE
DCOM- 20240304
LR  - 20240304
IS  - 1876-4479 (Electronic)
IS  - 1873-9946 (Linking)
VI  - 18
IP  - 3
DP  - 2024 Mar 1
TI  - Human Leukocyte Antigen Signatures as Pathophysiological Discriminants of 
      Microscopic Colitis Subtypes.
PG  - 349-359
LID - 10.1093/ecco-jcc/jjad165 [doi]
AB  - 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 x 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 x 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.
CI  - (c) The Author(s) 2023. Published by Oxford University Press on behalf of European 
      Crohn's and Colitis Organisation. All rights reserved. For permissions, please 
      email: journals.permissions@oup.com.
FAU - Zheng, Tenghao
AU  - Zheng T
AUID- ORCID: 0000-0003-1587-7481
AD  - School of Biological Sciences, Monash University, Clayton, VIC, Australia.
AD  - Clinical Epidemiology Division, Department of Medicine Solna, Karolinska 
      Institutet, Stockholm, Sweden.
AD  - Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
FAU - Roda, Giulia
AU  - Roda G
AD  - Biostructures and Biosystems National Institute, Rome, Italy.
FAU - Zabana, Yamile
AU  - Zabana Y
AUID- ORCID: 0000-0003-4023-8868
AD  - Gastroenterology Department, Hospital Universitari Mutua de Terrassa, Barcelona, 
      Spain.
AD  - Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas, 
      Barcelona, Spain.
FAU - Escudero-Hernandez, Celia
AU  - Escudero-Hernandez C
AD  - Department of Biomedical and Clinical Sciences, Linkoping University, Linkoping, 
      Sweden.
AD  - Institute of Clinical Molecular Biology, Kiel University and University Medical 
      Center Schleswig-Holstein, Kiel, Germany.
FAU - Liu, Xingrong
AU  - Liu X
AD  - Clinical Epidemiology Division, Department of Medicine Solna, Karolinska 
      Institutet, Stockholm, Sweden.
AD  - Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
FAU - Chen, Ye
AU  - Chen Y
AD  - Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA.
FAU - Camargo Tavares, Leticia
AU  - Camargo Tavares L
AUID- ORCID: 0000-0001-7278-0999
AD  - School of Biological Sciences, Monash University, Clayton, VIC, Australia.
FAU - Bonfiglio, Ferdinando
AU  - Bonfiglio F
AUID- ORCID: 0000-0003-2488-3867
AD  - School of Biological Sciences, Monash University, Clayton, VIC, Australia.
AD  - Clinical Epidemiology Division, Department of Medicine Solna, Karolinska 
      Institutet, Stockholm, Sweden.
FAU - Mellander, Marie-Rose
AU  - Mellander MR
AD  - Department of Clinical Sciences, Lund University, Lund, Sweden.
FAU - Janczewska, Izabella
AU  - Janczewska I
AD  - Medical Department, Ersta Hospital, Stockholm, Sweden.
FAU - Vigren, Lina
AU  - Vigren L
AD  - Department of Clinical Sciences, Lund University, Lund, Sweden.
FAU - Sjoberg, Klas
AU  - Sjoberg K
AD  - Department of Clinical Sciences, Lund University, Skane University Hospital, 
      Malmo, Sweden.
FAU - Ohlsson, Bodil
AU  - Ohlsson B
AUID- ORCID: 0000-0002-9142-5244
AD  - Department of Clinical Sciences, Lund University, Skane University Hospital, 
      Malmo, Sweden.
FAU - Almer, Sven
AU  - Almer S
AD  - Division of Gastroenterology, Department of Gastroenterology, Dermatology and 
      Rheumatology, Karolinska University Hospital, Stockholm, Sweden.
FAU - Halfvarson, Jonas
AU  - Halfvarson J
AUID- ORCID: 0000-0003-0122-7234
AD  - Department of Gastroenterology, Faculty of Medicine and Health, Orebro University 
      Hospital, Orebro, Sweden.
FAU - Miehlke, Stephan
AU  - Miehlke S
AD  - Centre for Digestive Diseases, Internal Medicine Centre Eppendorf, and Centre for 
      Oesophageal Disorders, University Hospital Eppendorf, Hamburg, Germany.
FAU - Madisch, Ahmed
AU  - Madisch A
AD  - Department of Gastroenterology, CRH Clinic Siloah, Hannover, Germany.
FAU - Lieb, Wolfgang
AU  - Lieb W
AD  - Institute of Epidemiology, Christian-Albrechts-University of Kiel, Kiel, Germany.
FAU - Kupcinskas, Juozas
AU  - Kupcinskas J
AD  - Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, 
      Lithuania.
FAU - Weersma, Rinse K
AU  - Weersma RK
AD  - Department of Gastroenterology and Hepatology, University of Groningen and 
      University Medical Center Groningen, Groningen, The Netherlands.
FAU - Bujanda, Luis
AU  - Bujanda L
AD  - Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas, 
      Barcelona, Spain.
AD  - Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research 
      Institute, Donostia University Hospital, Universidad del Pais Vasco, San 
      Sebastian, Spain.
FAU - Julia, Antonio
AU  - Julia A
AUID- ORCID: 0000-0001-6064-3620
AD  - Rheumatology Research Group, Vall d' Hebron Research Institute, Barcelona, Spain.
FAU - Marsal, Sara
AU  - Marsal S
AD  - Rheumatology Research Group, Vall d' Hebron Research Institute, Barcelona, Spain.
FAU - Esteve, Maria
AU  - Esteve M
AD  - Gastroenterology Department, Hospital Universitari Mutua de Terrassa, Barcelona, 
      Spain.
AD  - Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas, 
      Barcelona, Spain.
FAU - Guagnozzi, Danila
AU  - Guagnozzi D
AD  - Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas, 
      Barcelona, Spain.
AD  - Department of Gastroenterology, Vall d'Hebron University Hospital, 
      Neuro-Immuno-Gastroenterology Group, Digestive System Research Unit, Vall 
      d'Hebron Institut de Recerca, Barcelona, Spain.
FAU - Fernandez-Banares, Fernando
AU  - Fernandez-Banares F
AUID- ORCID: 0000-0002-1489-504X
AD  - Gastroenterology Department, Hospital Universitari Mutua de Terrassa, Barcelona, 
      Spain.
AD  - Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas, 
      Barcelona, Spain.
FAU - Ferrer, Carmen
AU  - Ferrer C
AD  - Pathology Department, Hospital Universitari Mutua de Terrassa, Barcelona, Spain.
CN  - MC-Europe GETECCU GWAS group
FAU - Peter, Inga
AU  - Peter I
AD  - Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount 
      Sinai, New York, NY, USA.
FAU - Ludvigsson, Jonas F
AU  - Ludvigsson JF
AD  - Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 
      Stockholm, Sweden.
FAU - Pardi, Darrell
AU  - Pardi D
AUID- ORCID: 0000-0003-0420-8784
AD  - Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
FAU - Verhaegh, Bas
AU  - Verhaegh B
AUID- ORCID: 0000-0002-2111-5363
AD  - Division Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM 
      School of Nutrition and Translational Research in Metabolism, Maastricht 
      University Medical Centre+, Maastricht, The Netherlands.
FAU - Jonkers, Daisy
AU  - Jonkers D
AD  - Division Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM 
      School of Nutrition and Translational Research in Metabolism, Maastricht 
      University Medical Centre+, Maastricht, The Netherlands.
FAU - Pierik, Marieke
AU  - Pierik M
AUID- ORCID: 0000-0001-6981-6516
AD  - Division Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM 
      School of Nutrition and Translational Research in Metabolism, Maastricht 
      University Medical Centre+, Maastricht, The Netherlands.
FAU - Munch, Andreas
AU  - Munch A
AUID- ORCID: 0000-0003-4703-581X
AD  - Department of Biomedical and Clinical Sciences, Linkoping University, Linkoping, 
      Sweden.
AD  - Department of Gastroenterology and Hepatology, Linkoping University, Linkoping, 
      Sweden.
AD  - Department of Health, Medicine, and Caring Sciences, Linkoping University, 
      Linkoping, Sweden.
FAU - Franke, Andre
AU  - Franke A
AD  - Institute of Clinical Molecular Biology, Kiel University and University Medical 
      Center Schleswig-Holstein, Kiel, Germany.
FAU - Bresso, Francesca
AU  - Bresso F
AD  - Division of Gastroenterology, Department of Gastroenterology, Dermatology and 
      Rheumatology, Karolinska University Hospital, Stockholm, Sweden.
FAU - Khalili, Hamed
AU  - Khalili H
AD  - Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA.
AD  - Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, 
      Boston, MA, USA.
AD  - Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, 
      MA, USA.
FAU - Colombel, Jean-Frederic
AU  - Colombel JF
AUID- ORCID: 0000-0001-6472-249X
AD  - Dr Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at 
      Mount Sinai, New York, NY, USA.
FAU - D'Amato, Mauro
AU  - D'Amato M
AUID- ORCID: 0000-0003-2743-5197
AD  - Clinical Epidemiology Division, Department of Medicine Solna, Karolinska 
      Institutet, Stockholm, Sweden.
AD  - Gastrointestinal Genetics Lab, CIC bioGUNE - BRTA, Derio, Spain.
AD  - Ikerbasque, Basque Foundation for Science, Bilbao, Spain.
AD  - Department of Medicine and Surgery, LUM University, Casamassima, Italy.
LA  - eng
GR  - VR 2017-02403/Swedish Research Council/
PT  - Journal Article
PT  - Meta-Analysis
PL  - England
TA  - J Crohns Colitis
JT  - Journal of Crohn's & colitis
JID - 101318676
RN  - 0 (HLA Antigens)
RN  - 0 (Histocompatibility Antigens Class II)
SB  - IM
CIN - J Crohns Colitis. 2024 Jan 04;:. PMID: 38174741
MH  - Humans
MH  - Genome-Wide Association Study
MH  - HLA Antigens/genetics
MH  - Histocompatibility Antigens Class II
MH  - *Colitis, Microscopic/genetics
MH  - *Colitis, Lymphocytic/genetics
MH  - *Colitis, Collagenous
OTO - NOTNLM
OT  - GWAS
OT  - HLA
OT  - Microscopic colitis
OT  - collagenous colitis
OT  - genetics
FIR - Zabana, Yamile
IR  - Zabana Y
FIR - Fernandez-Banares, Fernando
IR  - Fernandez-Banares F
FIR - Esteve, Maria
IR  - Esteve M
FIR - Piqueras, Marta
IR  - Piqueras M
FIR - Busquets, David
IR  - Busquets D
FIR - Iglesias, Eva
IR  - Iglesias E
FIR - Lucendo, Alfredo J
IR  - Lucendo AJ
EDAT- 2023/09/28 12:43
MHDA- 2024/03/04 06:45
CRDT- 2023/09/28 11:32
PHST- 2023/05/17 00:00 [received]
PHST- 2023/07/29 00:00 [revised]
PHST- 2023/09/26 00:00 [accepted]
PHST- 2024/03/04 06:45 [medline]
PHST- 2023/09/28 12:43 [pubmed]
PHST- 2023/09/28 11:32 [entrez]
AID - 7285336 [pii]
AID - 10.1093/ecco-jcc/jjad165 [doi]
PST - ppublish
SO  - J Crohns Colitis. 2024 Mar 1;18(3):349-359. doi: 10.1093/ecco-jcc/jjad165.