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Identification of susceptibility loci for Takayasu arteritis through a large multi-ancestral genome-wide association study.

Ortiz-Fernández L, Saruhan-Direskeneli G, Alibaz-Oner F et al.

33308445 PubMed ID
GWAS Study Type
6854 Participants
157 Views
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Chapter I

Publication Details

Comprehensive information about this research publication

Authors

OL
Ortiz-Fernández L
SG
Saruhan-Direskeneli G
AF
Alibaz-Oner F
KS
Kaymaz-Tahra S
CP
Coit P
KX
Kong X
KA
Kiprianos AP
MR
Maughan RT
AS
Aydin SZ
AK
Aksu K
KG
Keser G
KS
Kamali S
IM
Inanc M
SJ
Springer J
AS
Akar S
OF
Onen F
AN
Akkoc N
KN
Khalidi NA
KC
Koening C
KO
Karadag O
KS
Kiraz S
FL
Forbess L
LC
Langford CA
MC
McAlear CA
OZ
Ozbalkan Z
YS
Yavuz S
ÇG
Çetin GY
AN
Alpay-Kanitez N
CS
Chung S
AA
Ates A
KY
Karaaslan Y
MK
McKinnon-Maksimowicz K
MP
Monach PA
OH
Ozer HTE
SE
Seyahi E
FI
Fresko I
CA
Cefle A
SP
Seo P
WK
Warrington KJ
OM
Ozturk MA
YS
Ytterberg SR
CV
Cobankara V
OA
Onat AM
DN
Duzgun N
BM
Bıcakcıgil M
YS
Yentür SP
LL
Lally L
MA
Manfredi AA
BE
Baldissera E
EE
Erken E
YA
Yazici A
KB
Kısacık B
KT
Kaşifoğlu T
DE
Dalkilic E
CD
Cuthbertson D
PC
Pagnoux C
SA
Sreih A
RG
Reales G
WC
Wallace C
WJ
Wren JD
CD
Cunninghame-Graham DS
VT
Vyse TJ
SY
Sun Y
CH
Chen H
GP
Grayson PC
TE
Tombetti E
JL
Jiang L
MJ
Mason JC
MP
Merkel PA
DH
Direskeneli H
SA
Sawalha AH
Chapter II

Abstract

Summary of the research findings

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.

286 European ancestry cases, 2,652 European ancestry controls, 76 Han Chinese ancestry cases, 889 Han Chinese ancestry controls, 46 South Asian ancestry cases, 501 South Asian ancestry controls, 683 Turkish ancestry cases, 1,721 Turkish ancestry controls

Chapter III

Study Statistics

Key metrics and study information

6854
Total Participants
GWAS
Study Type
No
Replicated
Other, East Asian, South Asian, European
Ancestry
U.K.
Recruitment Country
Chapter IV

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