Open AccessIdentification of susceptibility loci for Takayasu arteritis through a large multi-ancestral genome-wide association study
Author(s) -
Lourdes OrtizFernández,
Güher SaruhanDireskeneli,
Fatma Alıbaz-Öner,
Sema Kaymaz Tahra,
Patrick Coit,
Xiufang Kong,
Allan Kiprianos,
Robert T. Maughan,
Sibel Zehra Aydın,
Kenan Aksu,
Gökhan Keser,
Sevil Kamalı,
Murat İnanç,
Jason Springer,
Servet Akar,
Fatoş Önen,
Nurullah Akkoç,
Nader Khalidi,
Curry L. Koening,
Ömer Karadağ,
Sedat Kiraz,
Lindsy Forbess,
Carol A. Langford,
Carol A. McAlear,
Zeynep Özbalkan,
Şule Yavuz,
Gözde Yıldırım Çetin,
Nilüfer Alpay Kanıtez,
Sharon A. Chung,
Aşkın Ateş,
Yaşar Karaaslan,
Kathleen McKin-Maksimowicz,
Paul A. Monach,
Hüseyin Özer,
Emire Seyahi,
İzzet Fresko,
Ayşe Çefle,
Philip Seo,
Kenneth J. Warrington,
Mehmet Akif Öztürk,
Steven R. Ytterberg,
Veli Çobankara,
Ahmet Mesut Onat,
Nurşen Düzgün,
Müge Bıçakçıgil,
Sibel P. Yentür,
Lindsay Lally,
Angelo A. Manfredi,
Elena Baldissera,
Eren Erken,
Ayten Yazıcı,
Bünyamin Kısacık,
Timuçin Kaşifoğlu,
Ediz Dalkılıç,
David Cuthbertson,
Christian Pagnoux,
Antoine G. Sreih,
Guillermo Reales,
Chris Wallace,
Jonathan D. Wren,
Deborah S. CunninghameGraham,
Timothy J. Vyse,
Ying Sun,
Huiyong Chen,
Peter C. Grayson,
Enrico Tombetti,
Lindi Jiang,
Justin C. Mason,
Peter A. Merkel,
Haner Di̇reskeneli̇,
Amr H. Sawalha
Publication year - 2020
Publication title -
the american journal of human genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.661
H-Index - 302
eISSN - 1537-6605
pISSN - 0002-9297
DOI - 10.1016/j.ajhg.2020.11.014
Subject(s) - genome wide association study , arteritis , genetic association , disease , takayasu's arteritis , biology , human leukocyte antigen , genetics , takayasu arteritis , candidate gene , gene , vasculitis , medicine , genotype , pathology , single nucleotide polymorphism , antigen
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 × 10 -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.
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