Identification of susceptibility loci for Takayasu arteritis through a large multi-ancestral genome-wide association study
Makaleler > Tam Makale · 2021
Yazarlar: Lourdes Ortiz-Fernandez, Guher Saruhan-Direskeneli, Fatma Alibaz Öner, Sema Kaymaz-Tahra, Patrick Coit, Xiufang Kong, Allan P. Kiprianos, Robert T. Maughan, Sibel Z. Aydin, Kenan AKSU, Gökhan KESER, Sevil Kamali, Murat Inanc, Jason Springer, Servet Akar, Fatoş Önen, Nurullah Akkoç, Nader A. Khalidi, Curry Koening, Ömer Karadağ, Sedat Kiraz, Lindsy Forbess, Carol A. Langford, Carol A. Mcalear, Zeynep Ozbalkan, Sule Yavuz, Gözde Yıldırım Çetin, Nilufer Alpay-Kanitez, Sharon Chung, Askin Ates, Yasar Karaaslan, Kathleen Mckinnon-Maksimowicz, Paul A. Monach, Huseyin T. E. Ozer, Emire Seyahi, İzzet Fresko, Ayşe Çefle, Philip Seo, Kenneth J. Warrington, Mehmet A. Ozturk, Steven R. Ytterberg, Veli Cobankara, Ahmet Mesut Onat, Nurşen Düzgün, Muge Bicakcigil, Sibel P. Yentur, Lindsay Lally, Angelo A. Manfredi, Elena Baldissera, Eren Erken, Ayten Yazıcı, Bunyamin Kisacik, Timuçin Kaşifoğlu, Hüseyin Ediz Dalkılıç, David Cuthbertson, Christian Pagnoux, Antoine Sreih, Guillermo Reales, Chris Wallace, Jonathan D. Wren, Deborah S. Cunninghame-Graham, Timothy J. Vyse, Ying Sun, Huiyong Chen, Peter C. Grayson, Enrico Tombetti, Lindi Jiang, Justin C. Mason, Peter A. Merkel, Rafi Haner Direskeneli, Amr H. Sawalha
AMERICAN JOURNAL OF HUMAN GENETICS, SCI Expanded İndekslerine Giren Dergi, Uluslararası, 2021, cilt 108, ss 84-99
DOI: 10.1016/j.ajhg.2020.11.014
Özet
Takayasu arteritis is a rare inflammatory disease of large arteries. We performed a genetic study in Takayasu arteritis comprising 6,670 individuals (1,226 affected individuals) from five different populations. We discovered HLA risk factors and four non-HLA susceptibility loci in VPS8, SVEP1, CFL2, and chr13q21 and reinforced IL12B, PTK2B, 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 < 5 x 10(-s)) 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.