Genome-wide association study of ankylosing spondylitis identifies non-MHC susceptibility loci.
To identify susceptibility loci for ankylosing spondylitis, we undertook a genome-wide association study in 2,053 unrelated ankylosing spondylitis cases among people of European descent and 5,140 ethnically matched controls, with replication in an independent cohort of 898 ankylosing spondylitis cases and 1,518 controls. Cases were genotyped with Illumina HumHap370 genotyping chips. In addition to strong association with the major histocompatibility complex (MHC; P < 10(-800)), we found association with SNPs in two gene deserts at 2p15 (rs10865331; combined P = 1.9 x 10(-19)) and 21q22 (rs2242944; P = 8.3 x 10(-20)), as well as in the genes ANTXR2 (rs4333130; P = 9.3 x 10(-8)) and IL1R2 (rs2310173; P = 4.8 x 10(-7)). We also replicated previously reported associations at IL23R (rs11209026; P = 9.1 x 10(-14)) and ERAP1 (rs27434; P = 5.3 x 10(-12)). This study reports four genetic loci associated with ankylosing spondylitis risk and identifies a major role for the interleukin (IL)-23 and IL-1 cytokine pathways in disease susceptibility.
University of Texas Health Science Center at Houston, USA.
Reveille
John D
JD
Sims
Anne-Marie
AM
Danoy
Patrick
P
Evans
David M
DM
Leo
Paul
P
Pointon
Jennifer J
JJ
Jin
Rui
R
Zhou
Xiaodong
X
Bradbury
Linda A
LA
Appleton
Louise H
LH
Davis
John C
JC
Diekman
Laura
L
Doan
Tracey
T
Dowling
Alison
A
Duan
Ran
R
Duncan
Emma L
EL
Farrar
Claire
C
Hadler
Johanna
J
Harvey
David
D
Karaderi
Tugce
T
Mogg
Rebecca
R
Pomeroy
Emma
E
Pryce
Karena
K
Taylor
Jacqueline
J
Savage
Laurie
L
Deloukas
Panos
P
Kumanduri
Vasudev
V
Peltonen
Leena
L
Ring
Sue M
SM
Whittaker
Pamela
P
Glazov
Evgeny
E
Thomas
Gethin P
GP
Maksymowych
Walter P
WP
Inman
Robert D
RD
Ward
Michael M
MM
Stone
Millicent A
MA
Weisman
Michael H
MH
Wordsworth
B Paul
BP
Brown
Matthew A
MA
D015331:Cohort Studies; D056426:Genetic Loci / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008285:Major Histocompatibility Complex / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015203:Reproducibility of Results; D013167:Spondylitis, Ankylosing / Q000235:genetics*