Genomewide scan of hoarding in sib pairs in which both sibs have Gilles de la Tourette syndrome

Abstract

A genome scan of the hoarding phenotype (a component of obsessive-compulsive disorder) was conducted on 77 sib pairs collected by the Tourette Syndrome Association International Consortium for Genetics (TSAICG). All sib pairs were concordant for a diagnosis of Gilles de la Tourette syndrome (GTS). However, the analyses reported here were conducted for hoarding as both a dichotomous trait and a quantitative trait. Not all sib pairs in the sample were concordant for hoarding. Standard linkage analyses were performed using GENEHUNTER and Haseman-Elston methods. In addition, novel analyses with a recursive-partitioning technique were employed. Significant allele sharing was observed for both the dichotomous and the quantitative hoarding phenotypes for markers at 4q34-35 (P = .0007), by use of GENEHUNTER, and at 5q35.2-35.3 (P = .000002) and 17q25 (P = .00002), by use of the revisited Haseman-Elston method. The 4q site is in proximity to D4S1625, which was identified by the TSAICG as a region linked to the GTS phenotype. The recursive-partitioning technique examined multiple markers simultaneously. Results suggest joint effects of specific loci on 5q and 4q, with an overall P value of .000003. Although P values were not adjusted for multiple comparison, nearly all were much smaller than the customary significance level of .0001 for genomewide scans. © 2002 Elsevier Science Ltd. All rights reserved.