TY - JOUR
T1 - Linkage heterogeneity for the IBD1 locus in Crohn's disease pedigrees by disease onset and severity
AU - Brant, Steven R.
AU - Panhuysen, Carolien I.M.
AU - Bailey-Wilson, Joan E.
AU - Rohal, Patrick M.
AU - Lee, Sinda
AU - Mann, Jasdeep
AU - Ravenhill, Geoffrey
AU - Kirschner, Barbara S.
AU - Hanauer, Stephen B.
AU - Cho, Judy H.
AU - Bayless, Theodore M.
PY - 2000
Y1 - 2000
N2 - Background & Aims: There is evidence for the IBD1 Crohn's disease (CD) susceptibility locus on chromosome 16 in several but not all populations studied. Genetic and phenotypic heterogeneity may underlie ability to replicate IBD1. We determined if age and severity stratification could identify a clinical subgroup at risk for IBD1. Methods: Linkage analysis at microsatellites spanning chromosome 16 was performed in 2 groups of CD pedigrees: group 1, 57 pedigrees with at least one affected relative classified as having "severe" disease, by history of surgical resection or immunomodulator therapy, and with disease diagnosed before age 22; and group 2, 33 pedigrees with no history of early-onset, severe CD. Results: Group 1 pedigrees demonstrated genomewide significant linkage evidence for the IBD1 locus (nonparametric multipoint logarithm of the odds [Mlod], 3.84; P = 1.3 × 10-5) with linkage evidence greater than all 90 pedigrees (Mlod, 2.12; P = 9.0 × 10-4). Group 2 pedigrees had near zero nonparametric 2-point and Mlod scores for the IBD1 region. Heterogeneity between groups 1 and 2 was significant (P = 0.002). Conclusions: Presence of early-onset, more severe CD identifies pedigrees at high risk for IBD1. These pedigrees will have more power to refine the IBD1 locus and identify the causative gene.
AB - Background & Aims: There is evidence for the IBD1 Crohn's disease (CD) susceptibility locus on chromosome 16 in several but not all populations studied. Genetic and phenotypic heterogeneity may underlie ability to replicate IBD1. We determined if age and severity stratification could identify a clinical subgroup at risk for IBD1. Methods: Linkage analysis at microsatellites spanning chromosome 16 was performed in 2 groups of CD pedigrees: group 1, 57 pedigrees with at least one affected relative classified as having "severe" disease, by history of surgical resection or immunomodulator therapy, and with disease diagnosed before age 22; and group 2, 33 pedigrees with no history of early-onset, severe CD. Results: Group 1 pedigrees demonstrated genomewide significant linkage evidence for the IBD1 locus (nonparametric multipoint logarithm of the odds [Mlod], 3.84; P = 1.3 × 10-5) with linkage evidence greater than all 90 pedigrees (Mlod, 2.12; P = 9.0 × 10-4). Group 2 pedigrees had near zero nonparametric 2-point and Mlod scores for the IBD1 region. Heterogeneity between groups 1 and 2 was significant (P = 0.002). Conclusions: Presence of early-onset, more severe CD identifies pedigrees at high risk for IBD1. These pedigrees will have more power to refine the IBD1 locus and identify the causative gene.
UR - http://www.scopus.com/inward/record.url?scp=0034464007&partnerID=8YFLogxK
U2 - 10.1053/gast.2000.20245
DO - 10.1053/gast.2000.20245
M3 - Article
C2 - 11113069
AN - SCOPUS:0034464007
SN - 0016-5085
VL - 119
SP - 1483
EP - 1490
JO - Gastroenterology
JF - Gastroenterology
IS - 6
ER -