Investigation of reported associations between the 20q13 and 21q22 loci and pediatric-onset Crohn's disease in Canadian children.
OBJECTIVE
A recent pediatric-focused genome-wide association study has reported novel associations of the 20q13 and 21q22 loci with inflammatory bowel disease (IBD). We aimed to investigate these associations with Crohn's disease (CD) in Canadian children.


METHODS
A combined case-control and case-parent design was implemented at three pediatric gastroenterology clinics in Canada. Children less than 20 years of age with a confirmed diagnosis of CD were recruited along with controls. For a subset of the patients, biological parents were also recruited. Three single-nucleotide polymorphisms (SNPs) at the 20q13 locus and 1 SNP at the 21q22 locus were genotyped. Associations between individual SNPs and haplotypes were examined.


RESULTS
A total of 410 cases, 415 controls, and 302 parents were studied. The mean (+/-s.d.) age for the cases was 12.3 (+/-3.2) years. Most cases were men (56.1%) who had ileocolonic disease (L3+/-L4, 52.2%) and inflammatory behavior (B1+/-B4, 87.0%) at diagnosis. Single SNP analysis showed that all 3 SNPs at the 20q13 locus were significantly associated with CD (rs2297441, P=2.24x10(-4); rs2315008, P=4.77x10(-4); rs4809330, P=6.08x10(-3)). Haplotype analysis suggested that the association signal at 20q13 resided on a common haplotype comprising the minor allele of rs2297441 (P=2.8x10(-5)). SNP rs2836878 at the 21q22 locus showed a trend for association with CD that was statistically not significant (P=0.06).


CONCLUSIONS
Our results support an association between the 20q13 locus and CD in Canadian children. Positional cloning studies are required to further dissect the potential causative genes in the region.
Amre
Devendra K
DK
Department of Pediatrics, University of Montreal, Montreal, Canada. devendra.amre@umontreal.ca
Mack
David R
DR
Morgan
Kenneth
K
Fujiwara
Mary
M
Israel
David
D
Deslandres
Colette
C
Seidman
Ernest G
EG
Lambrette
Phlippe
P
Costea
Irina
I
Krupoves
Alfreda
A
Fegury
Houda
H
Dong
Jinsong
J
Grimard
Guy
G
Levy
Emile
E
D000293:Adolescent; D017677:Age Distribution; D017668:Age of Onset; D002170:Canada / Q000453:epidemiology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics*; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D015331:Cohort Studies; D016001:Confidence Intervals; D003424:Crohn Disease / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015994:Incidence; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values; D018570:Risk Assessment; D017678:Sex Distribution