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.
McGovern
Dermot P B
DP
Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA. mcgovernd@cshs.org
Gardet
Agnès
A
Törkvist
Leif
L
Goyette
Philippe
P
Essers
Jonah
J
Taylor
Kent D
KD
Neale
Benjamin M
BM
Ong
Rick T H
RT
Lagacé
Caroline
C
Li
Chun
C
Green
Todd
T
Stevens
Christine R
CR
Beauchamp
Claudine
C
Fleshner
Phillip R
PR
Carlson
Marie
M
D'Amato
Mauro
M
Halfvarson
Jonas
J
Hibberd
Martin L
ML
Lördal
Mikael
M
Padyukov
Leonid
L
Andriulli
Angelo
A
Colombo
Elisabetta
E
Latiano
Anna
A
Palmieri
Orazio
O
Bernard
Edmond-Jean
EJ
Deslandres
Colette
C
Hommes
Daan W
DW
de Jong
Dirk J
DJ
Stokkers
Pieter C
PC
Weersma
Rinse K
RK
Sharma
Yashoda
Y
Silverberg
Mark S
MS
Cho
Judy H
JH
Wu
Jing
J
Roeder
Kathryn
K
Brant
Steven R
SR
Schumm
L Phillip
LP
Duerr
Richard H
RH
Dubinsky
Marla C
MC
Glazer
Nicole L
NL
Haritunians
Talin
T
Ippoliti
Andy
A
Melmed
Gil Y
GY
Siscovick
David S
DS
Vasiliauskas
Eric A
EA
Targan
Stephan R
SR
Annese
Vito
V
Wijmenga
Cisca
C
Pettersson
Sven
S
Rotter
Jerome I
JI
Xavier
Ramnik J
RJ
Daly
Mark J
MJ
Rioux
John D
JD
Seielstad
Mark
M
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