Genomewide search in Canadian families with inflammatory bowel disease reveals two novel susceptibility loci.
The chronic inflammatory bowel diseases (IBDs)-Crohn disease (CD) and ulcerative colitis (UC)-are idiopathic, inflammatory disorders of the gastrointestinal tract. These conditions have a peak incidence in early adulthood and a combined prevalence of approximately 100-200/100,000. Although the etiology of IBD is multifactorial, a significant genetic contribution to disease susceptibility is implied by epidemiological data revealing a sibling risk of approximately 35-fold for CD and approximately 15-fold for UC. To elucidate the genetic basis for these disorders, we undertook a genomewide scan in 158 Canadian sib-pair families and identified three regions of suggestive linkage (3p, 5q31-33, and 6p) and one region of significant linkage to 19p13 (LOD score 4.6). Higher-density mapping in the 5q31-q33 region revealed a locus of genomewide significance (LOD score 3.9) that contributes to CD susceptibility in families with early-onset disease. Both of these genomic regions contain numerous genes that are important to the immune and inflammatory systems and that provide good targets for future candidate-gene studies.
Rioux
J D
JD
Whitehead Institute/Massachusetts Institute of Technology, Center for Genome Research, Cambridge, MA 02139, USA. rioux@genome.wi.mit.edu
Silverberg
M S
MS
Daly
M J
MJ
Steinhart
A H
AH
McLeod
R S
RS
Griffiths
A M
AM
Green
T
T
Brettin
T S
TS
Stone
V
V
Bull
S B
SB
Bitton
A
A
Williams
C N
CN
Greenberg
G R
GR
Cohen
Z
Z
Lander
E S
ES
Hudson
T J
TJ
Siminovitch
K A
KA
D017668:Age of Onset; D002170:Canada; D002874:Chromosome Mapping; D002877:Chromosomes, Human / Q000235:genetics; D003093:Colitis, Ulcerative / Q000235:genetics*; D003424:Crohn Disease / Q000453:epidemiology / Q000235:genetics*; D008040:Genetic Linkage / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007585:Jews / Q000235:genetics; D008126:Lod Score; D016555:Matched-Pair Analysis; D009679:Nuclear Family; D010375:Pedigree; D010641:Phenotype