Genome-wide association identifies multiple ulcerative colitis susceptibility loci.
Ulcerative colitis is a chronic, relapsing inflammatory condition of the gastrointestinal tract with a complex genetic and environmental etiology. In an effort to identify genetic variation underlying ulcerative colitis risk, we present two distinct genome-wide association studies of ulcerative colitis and their joint analysis with a previously published scan, comprising, in aggregate, 2,693 individuals with ulcerative colitis and 6,791 control subjects. Fifty-nine SNPs from 14 independent loci attained an association significance of P < 10(-5). Seven of these loci exceeded genome-wide significance (P < 5 x 10(-8)). After testing an independent cohort of 2,009 cases of ulcerative colitis and 1,580 controls, we identified 13 loci that were significantly associated with ulcerative colitis (P < 5 x 10(-8)), including the immunoglobulin receptor gene FCGR2A, 5p15, 2p16 and ORMDL3 (orosomucoid1-like 3). We confirmed association with 14 previously identified ulcerative colitis susceptibility loci, and an analysis of acknowledged Crohn's disease loci showed that roughly half of the known Crohn's disease associations are shared with ulcerative colitis. These data implicate approximately 30 loci in ulcerative colitis, thereby providing insight into disease pathogenesis.
Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA. mcgovernd@cshs.org
Dermot P B
DP
McGovern
Agnès
A
Gardet
Leif
L
Törkvist
Philippe
P
Goyette
Jonah
J
Essers
Kent D
KD
Taylor
Benjamin M
BM
Neale
Rick T H
RT
Ong
Caroline
C
Lagacé
Chun
C
Li
Todd
T
Green
Christine R
CR
Stevens
Claudine
C
Beauchamp
Phillip R
PR
Fleshner
Marie
M
Carlson
Mauro
M
D'Amato
Jonas
J
Halfvarson
Martin L
ML
Hibberd
Mikael
M
Lördal
Leonid
L
Padyukov
Angelo
A
Andriulli
Elisabetta
E
Colombo
Anna
A
Latiano
Orazio
O
Palmieri
Edmond-Jean
EJ
Bernard
Colette
C
Deslandres
Daan W
DW
Hommes
Dirk J
DJ
de Jong
Pieter C
PC
Stokkers
Rinse K
RK
Weersma
Yashoda
Y
Sharma
Mark S
MS
Silverberg
Judy H
JH
Cho
Jing
J
Wu
Kathryn
K
Roeder
Steven R
SR
Brant
L Phillip
LP
Schumm
Richard H
RH
Duerr
Marla C
MC
Dubinsky
Nicole L
NL
Glazer
Talin
T
Haritunians
Andy
A
Ippoliti
Gil Y
GY
Melmed
David S
DS
Siscovick
Eric A
EA
Vasiliauskas
Stephan R
SR
Targan
Vito
V
Annese
Cisca
C
Wijmenga
Sven
S
Pettersson
Jerome I
JI
Rotter
Ramnik J
RJ
Xavier
Mark J
MJ
Daly
John D
JD
Rioux
Mark
M
Seielstad
D003093:Colitis, Ulcerative / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D015201:Meta-Analysis as Topic; D020641:Polymorphism, Single Nucleotide; D017452:Receptors, IgG / Q000235:genetics
C445323:FCGR2A protein, human; D008565:Membrane Proteins; C464399:ORMDL3 protein, human; D017452:Receptors, IgG