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.

Figure 1

Nonparametric Z scores produced by GENEHUNTER for original and residual hoarding factor scores on chromosomes 4q (top), 5q (middle), and 17q (bottom).

Figure 2

Tree-based genome scan for linkage to hoarding. Nodes are labeled “1”–“7.” Inside each node, the numbers of sib pairs in which both members are affected (top number), only one member is affected (middle number), and neither member is affected (bottom number) are given. Thus, the three numbers indicate, from top to bottom, the numbers of both affected, discordant, and both unaffected pairs in any given node. IBD sharing is used to split nodes. Selected markers and cut-off values are below and to the bottom right of the node, respectively. P values calculated using Fisher’s exact test are presented for each node split and for the distribution among all terminal nodes (boxes).