Common variants at five new loci associated with early-onset inflammatory bowel disease.
The inflammatory bowel diseases (IBD) Crohn's disease and ulcerative colitis are common causes of morbidity in children and young adults in the western world. Here we report the results of a genome-wide association study in early-onset IBD involving 3,426 affected individuals and 11,963 genetically matched controls recruited through international collaborations in Europe and North America, thereby extending the results from a previous study of 1,011 individuals with early-onset IBD. We have identified five new regions associated with early-onset IBD susceptibility, including 16p11 near the cytokine gene IL27 (rs8049439, P = 2.41 x 10(-9)), 22q12 (rs2412973, P = 1.55 x 10(-9)), 10q22 (rs1250550, P = 5.63 x 10(-9)), 2q37 (rs4676410, P = 3.64 x 10(-8)) and 19q13.11 (rs10500264, P = 4.26 x 10(-10)). Our scan also detected associations at 23 of 32 loci previously implicated in adult-onset Crohn's disease and at 8 of 17 loci implicated in adult-onset ulcerative colitis, highlighting the close pathogenetic relationship between early- and adult-onset IBD.
Imielinski
Marcin
M
Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Baldassano
Robert N
RN
Griffiths
Anne
A
Russell
Richard K
RK
Annese
Vito
V
Dubinsky
Marla
M
Kugathasan
Subra
S
Bradfield
Jonathan P
JP
Walters
Thomas D
TD
Sleiman
Patrick
P
Kim
Cecilia E
CE
Muise
Aleixo
A
Wang
Kai
K
Glessner
Joseph T
JT
Saeed
Shehzad
S
Zhang
Haitao
H
Frackelton
Edward C
EC
Hou
Cuiping
C
Flory
James H
JH
Otieno
George
G
Chiavacci
Rosetta M
RM
Grundmeier
Robert
R
Castro
Massimo
M
Latiano
Anna
A
Dallapiccola
Bruno
B
Stempak
Joanne
J
Abrams
Debra J
DJ
Taylor
Kent
K
McGovern
Dermot
D
Silber
Gary
G
Wrobel
Iwona
I
Quiros
Antonio
A
Barrett
Jeffrey C
JC
Hansoul
Sarah
S
Nicolae
Dan L
DL
Cho
Judy H
JH
Duerr
Richard H
RH
Rioux
John D
JD
Brant
Steven R
SR
Silverberg
Mark S
MS
Taylor
Kent D
KD
Barmuda
M Michael
MM
Bitton
Alain
A
Dassopoulos
Themistocles
T
Datta
Lisa Wu
LW
Green
Todd
T
Griffiths
Anne M
AM
Kistner
Emily O
EO
Murtha
Michael T
MT
Regueiro
Miguel D
MD
Rotter
Jerome I
JI
Schumm
L Philip
LP
Steinhart
A Hillary
AH
Targan
Stephen R
SR
Xavier
Ramnik J
RJ
Libioulle
Cécile
C
Sandor
Cynthia
C
Lathrop
Mark
M
Belaiche
Jacques
J
Dewit
Olivier
O
Gut
Ivo
I
Heath
Simon
S
Laukens
Debby
D
Mni
Myriam
M
Rutgeerts
Paul
P
Van Gossum
André
A
Zelenika
Diana
D
Franchimont
Denis
D
Hugot
J P
JP
de Vos
Martine
M
Vermeire
Severine
S
Louis
Edouard
E
Cardon
Lon R
LR
Anderson
Carl A
CA
Drummond
Hazel
H
Nimmo
Elaine
E
Ahmad
Tariq
T
Prescott
Natalie J
NJ
Onnie
Clive M
CM
Fisher
Sheila A
SA
Marchini
Jonathan
J
Ghori
Jilur
J
Bumpstead
Suzannah
S
Gwillam
Rhian
R
Tremelling
Mark
M
Delukas
Panos
P
Mansfield
John
J
Jewell
Derek
D
Satsangi
Jack
J
Mathew
Christopher G
CG
Parkes
Miles
M
Georges
Michel
M
Daly
Mark J
MJ
Heyman
Melvin B
MB
Ferry
George D
GD
Kirschner
Barbara
B
Lee
Jessica
J
Essers
Jonah
J
Grand
Richard
R
Stephens
Michael
M
Levine
Arie
A
Piccoli
David
D
Van Limbergen
John
J
Cucchiara
Salvatore
S
Monos
Dimitri S
DS
Guthery
Stephen L
SL
Denson
Lee
L
Wilson
David C
DC
Grant
Straun F A
SF
Daly
Mark
M
Silverberg
Mark S
MS
Satsangi
Jack
J
Hakonarson
Hakon
H
D017668:Age of Onset; D002874:Chromosome Mapping; D003093:Colitis, Ulcerative / Q000235:genetics; D014644:Genetic Variation; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000453:epidemiology / Q000235:genetics*