Ulcerative colitis-risk loci on chromosomes 1p36 and 12q15 found by genome-wide association study.
Ulcerative colitis is a chronic inflammatory disease of the colon that presents as diarrhea and gastrointestinal bleeding. We performed a genome-wide association study using DNA samples from 1,052 individuals with ulcerative colitis and preexisting data from 2,571 controls, all of European ancestry. In an analysis that controlled for gender and population structure, ulcerative colitis loci attaining genome-wide significance and subsequent replication in two independent populations were identified on chromosomes 1p36 (rs6426833, combined P = 5.1 x 10(-13), combined odds ratio OR = 0.73) and 12q15 (rs1558744, combined P = 2.5 x 10(-12), combined OR = 1.35). In addition, combined genome-wide significant evidence for association was found in a region spanning BTNL2 to HLA-DQB1 on chromosome 6p21 (rs2395185, combined P = 1.0 x 10(-16), combined OR = 0.66) and at the IL23R locus on chromosome 1p31 (rs11209026, combined P = 1.3 x 10(-8), combined OR = 0.56; rs10889677, combined P = 1.3 x 10(-8), combined OR = 1.29).
Silverberg
Mark S
MS
Mount Sinai Hospital Inflammatory Bowel Disease Group, University of Toronto, 600 University Avenue, Toronto, ON M5G1X5, Canada.
Cho
Judy H
JH
Rioux
John D
JD
McGovern
Dermot P B
DP
Wu
Jing
J
Annese
Vito
V
Achkar
Jean-Paul
JP
Goyette
Philippe
P
Scott
Regan
R
Xu
Wei
W
Barmada
M Michael
MM
Klei
Lambertus
L
Daly
Mark J
MJ
Abraham
Clara
C
Bayless
Theodore M
TM
Bossa
Fabrizio
F
Griffiths
Anne M
AM
Ippoliti
Andrew F
AF
Lahaie
Raymond G
RG
Latiano
Anna
A
Paré
Pierre
P
Proctor
Deborah D
DD
Regueiro
Miguel D
MD
Steinhart
A Hillary
AH
Targan
Stephan R
SR
Schumm
L Philip
LP
Kistner
Emily O
EO
Lee
Annette T
AT
Gregersen
Peter K
PK
Rotter
Jerome I
JI
Brant
Steven R
SR
Taylor
Kent D
KD
Roeder
Kathryn
K
Duerr
Richard H
RH
D000071797:Butyrophilins; D016022:Case-Control Studies; D002878:Chromosomes, Human, Pair 1; D002881:Chromosomes, Human, Pair 12; D002896:Chromosomes, Human, Pair 6; D003093:Colitis, Ulcerative / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics; D059866:HLA-DQ beta-Chains; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D018123:Receptors, Interleukin / Q000235:genetics; D011995:Recombination, Genetic; D012307:Risk Factors
C408263:BTNL2 protein, human; D000071797:Butyrophilins; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; C515500:IL23R protein, human; D008562:Membrane Glycoproteins; D018123:Receptors, Interleukin