Identification of susceptibility loci for Takayasu arteritis through a large multi-ancestral genome-wide association study.
Authors
Ortiz-Fernández, Lourdes
Saruhan-Direskeneli, Güher
Alibaz-Oner, Fatma
Kaymaz-Tahra, Sema
Coit, Patrick
Kong, Xiufang
Kiprianos, Allan P
Maughan, Robert T
Aydin, Sibel Z
Aksu, Kenan
Keser, Gokhan
Kamali, Sevil
Inanc, Murat
Springer, Jason
Akar, Servet
Onen, Fatos
Akkoc, Nurullah
Khalidi, Nader A
Koening, Curry
Karadag, Omer
Kiraz, Sedat
Forbess, Lindsy
Langford, Carol A
McAlear, Carol A
Ozbalkan, Zeynep
Yavuz, Sule
Çetin, Gozde Yildirim
Alpay-Kanitez, Nilufer
Chung, Sharon
Ates, Askin
Karaaslan, Yasar
McKinnon-Maksimowicz, Kathleen
Monach, Paul A
Ozer, Hüseyin TE
Seyahi, Emire
Fresko, Izzet
Cefle, Ayse
Seo, Philip
Warrington, Kenneth J
Ozturk, Mehmet A
Ytterberg, Steven R
Cobankara, Veli
Onat, Ahmet Mesut
Duzgun, Nurşen
Bıcakcıgil, Muge
Yentür, Sibel P
Lally, Lindsay
Manfredi, Angelo A
Baldissera, Elena
Erken, Eren
Yazici, Ayten
Kısacık, Bünyamin
Kaşifoğlu, Timuçin
Dalkilic, Ediz
Cuthbertson, David
Pagnoux, Christian
Sreih, Antoine
Reales, Guillermo
Wren, Jonathan D
Cunninghame-Graham, Deborah S
Vyse, Timothy J
Sun, Ying
Chen, Huiyong
Grayson, Peter C
Tombetti, Enrico
Jiang, Lindi
Mason, Justin C
Merkel, Peter A
Direskeneli, Haner
Sawalha, Amr H
Publication Date
2021-01Journal Title
American journal of human genetics
ISSN
0002-9297
Publisher
Cell Press
Volume
108
Issue
1
Pages
84-99
Language
eng
Type
Article
This Version
AM
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
Ortiz-Fernández, L., Saruhan-Direskeneli, G., Alibaz-Oner, F., Kaymaz-Tahra, S., Coit, P., Kong, X., Kiprianos, A. P., et al. (2021). Identification of susceptibility loci for Takayasu arteritis through a large multi-ancestral genome-wide association study.. American journal of human genetics, 108 (1), 84-99. https://doi.org/10.1016/j.ajhg.2020.11.014
Abstract
Takayasu arteritis is a rare inflammatory disease of large arteries. We performed a genetic study in Takayasu arteritis comprising 6,670 individuals (1,226 cases) from five different populations. We revealed previously unreported HLA risk factors and four novel non-HLA susceptibility loci in VPS8, SVEP1, CFL2, and chr13q21, and reinforced IL12B, PTPK2B, and chr21q22 as robust susceptibility loci shared across ancestries. Functional analysis proposed plausible underlying disease mechanisms and pinpointed ETS2 as a potential causal gene for chr21q22 association. We also identified >60 candidate loci with suggestive association (p< 5X10-5) and devised a genetic risk score for Takayasu arteritis. Takayasu arteritis was compared to hundreds of other traits, revealing the closest genetic relatedness to inflammatory bowel disease. Epigenetic patterns within risk loci suggest roles for monocytes and B cells in Takayasu arteritis. This work enhances understanding of the genetic basis and pathophysiology of Takayasu arteritis and provides clues for potential new therapeutic targets.
Sponsorship
WELLCOME TRUST (107881/Z/15/Z)
Medical Research Council (MC_UU_00002/4)
Embargo Lift Date
2021-06-03
Identifiers
External DOI: https://doi.org/10.1016/j.ajhg.2020.11.014
This record's URL: https://www.repository.cam.ac.uk/handle/1810/313440
Rights
Attribution-NonCommercial-NoDerivatives 4.0 International
Licence URL: https://creativecommons.org/licenses/by-nc-nd/4.0/