title: Genomewide search in Canadian families with inflammatory bowel disease reveals two novel susceptibility loci.
abstract: 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.
authors.affiliation: Whitehead Institute/Massachusetts Institute of Technology, Center for Genome Research, Cambridge, MA 02139, USA. rioux@genome.wi.mit.edu
authors.forename: J D
authors.initials: JD
authors.lastname: Rioux
authors.forename: M S
authors.initials: MS
authors.lastname: Silverberg
authors.forename: M J
authors.initials: MJ
authors.lastname: Daly
authors.forename: A H
authors.initials: AH
authors.lastname: Steinhart
authors.forename: R S
authors.initials: RS
authors.lastname: McLeod
authors.forename: A M
authors.initials: AM
authors.lastname: Griffiths
authors.forename: T
authors.initials: T
authors.lastname: Green
authors.forename: T S
authors.initials: TS
authors.lastname: Brettin
authors.forename: V
authors.initials: V
authors.lastname: Stone
authors.forename: S B
authors.initials: SB
authors.lastname: Bull
authors.forename: A
authors.initials: A
authors.lastname: Bitton
authors.forename: C N
authors.initials: CN
authors.lastname: Williams
authors.forename: G R
authors.initials: GR
authors.lastname: Greenberg
authors.forename: Z
authors.initials: Z
authors.lastname: Cohen
authors.forename: E S
authors.initials: ES
authors.lastname: Lander
authors.forename: T J
authors.initials: TJ
authors.lastname: Hudson
authors.forename: K A
authors.initials: KA
authors.lastname: Siminovitch
mesh_terms: 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