Please use this identifier to cite or link to this item: https://www.um.edu.mt/library/oar/handle/123456789/120435
Title: Transethnic analysis of the human leukocyte antigen region for ulcerative colitis reveals not only shared but also ethnicity-specific disease associations
Authors: Degenhardt, Frauke
Mayr, Gabriele
Wendorff, Mareike
Boucher, Gabrielle
Ellinghaus, Eva
Ellinghaus, David
ElAbd, Hesham
Rosati, Elisa
Hübenthal, Matthias
Juzenas, Simonas
Abedian, Shifteh
Vahedi, Homayon
Thelma, BK
Yang, Suk-Kyun
Duk Ye, Byong
Cheon, Jae Hee
Daryani, Naser Ebrahim
Datta, Lisa Wu
Ellul, Pierre
Esaki, Motohiro
Fuyuno, Yuta
McGovern, Dermot P.B.
Haritunians, Talin
Hong, Myhunghee
Juyal, Garima
Jung, Eun Suk
Kubo, Michiaki
Kugathasan, Subra
Lenz, Tobias L.
Leslie, Stephen
Malekzadeh, Reza
Midha, Vandana
Motyer, Allan
Ng, Siew C.
Okou, David T.
Raychaudhuri, Soumya
Schembri, John
Schreiber, Stefan
Song, Kyuyoung
Sood, Ajit
Takahashi, Atsushi
Torres, Esther A.
Umeno, Junji
Alizadeh, Behrooz Z.
Weersma, Rinse K.
Wong, Sunny H.
Yamazaki, Keiko
Karlsen, Tom H.
Rioux, John D.
Brant, Steven R.
Franke, Andre
Authors: MAAIS Recruitment Center
International IBD Genetics Consortium
Keywords: Inflammatory bowel diseases
Crohn's disease
Ulcerative colitis
Leucocytes
Issue Date: 2021
Publisher: Oxford University Press
Citation: Degenhardt, F., Mayr, G., Wendorff, M., Boucher, G., Ellinghaus, E., Ellinghaus, D.,...International IBD Genetics Consortium. (2021). Transethnic analysis of the human leukocyte antigen region for ulcerative colitis reveals not only shared but also ethnicity-specific disease associations. Human molecular genetics, 30(5), 356-369.
Abstract: Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gut. Genetic association studies have identified the highly variable human leukocyte antigen (HLA) region as the strongest susceptibility locus for IBD and specifically DRB1∗01:03 as a determining factor for ulcerative colitis (UC). However, for most of the association signal such as delineation could not be made because of tight structures of linkage disequilibrium within the HLA. The aim of this study was therefore to further characterize the HLA signal using a transethnic approach. We performed a comprehensive fine mapping of single HLA alleles in UC in a cohort of 9272 individuals with African American, East Asian, Puerto Rican, Indian and Iranian descent and 40 691 previously analyzed Caucasians, additionally analyzing whole HLA haplotypes. We computationally characterized the binding of associated HLA alleles to human self-peptides and analyzed the physicochemical properties of the HLA proteins and predicted self-peptidomes. Highlighting alleles of the HLA-DRB1∗15 group and their correlated HLA-DQ-DR haplotypes, we not only identified consistent associations (regarding effects directions/magnitudes) across different ethnicities but also identified population-specific signals (regarding differences in allele frequencies). We observed that DRB1∗01:03 is mostly present in individuals of Western European descent and hardly present in non-Caucasian individuals. We found peptides predicted to bind to risk HLA alleles to be rich in positively charged amino acids. We conclude that the HLA plays an important role for UC susceptibility across different ethnicities. This research further implicates specific features of peptides that are predicted to bind risk and protective HLA proteins.
URI: https://www.um.edu.mt/library/oar/handle/123456789/120435
Appears in Collections:Scholarly Works - FacM&SMed



Items in OAR@UM are protected by copyright, with all rights reserved, unless otherwise indicated.