Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn's disease susceptibility.
A genome-wide association scan in individuals with Crohn's disease by the Wellcome Trust Case Control Consortium detected strong association at four novel loci. We tested 37 SNPs from these and other loci for association in an independent case-control sample. We obtained replication for the autophagy-inducing IRGM gene on chromosome 5q33.1 (replication P = 6.6 x 10(-4), combined P = 2.1 x 10(-10)) and for nine other loci, including NKX2-3, PTPN2 and gene deserts on chromosomes 1q and 5p13.
Parkes
Miles
M
Inflammatory Bowel Disease Research Group, Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 2QQ, UK. miles.parkes@addenbrookes.nhs.uk
Barrett
Jeffrey C
JC
Prescott
Natalie J
NJ
Tremelling
Mark
M
Anderson
Carl A
CA
Fisher
Sheila A
SA
Roberts
Roland G
RG
Nimmo
Elaine R
ER
Cummings
Fraser R
FR
Soars
Dianne
D
Drummond
Hazel
H
Lees
Charlie W
CW
Khawaja
Saud A
SA
Bagnall
Richard
R
Burke
Denis A
DA
Todhunter
Catherine E
CE
Ahmad
Tariq
T
Onnie
Clive M
CM
McArdle
Wendy
W
Strachan
David
D
Bethel
Graeme
G
Bryan
Claire
C
Lewis
Cathryn M
CM
Deloukas
Panos
P
Forbes
Alastair
A
Sanderson
Jeremy
J
Jewell
Derek P
DP
Satsangi
Jack
J
Mansfield
John C
JC
Cardon
Lon
L
Mathew
Christopher G
CG
D000818:Animals; D001343:Autophagy / Q000235:genetics*; D016022:Case-Control Studies; D003424:Crohn Disease / Q000235:genetics*; D019204:GTP-Binding Proteins / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D051379:Mice; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA
D019204:GTP-Binding Proteins; C513539:IRGM protein, human