title: Linkage analysis for autism in a subset families with obsessive-compulsive behaviors: evidence for an autism susceptibility gene on chromosome 1 and further support for susceptibility genes on chromosome 6 and 19.
abstract: Although there is considerable evidence for a strong genetic component to idiopathic autism, several genome-wide screens for susceptibility genes have been carried out with limited concordance of linked loci, reflecting numerous genes of weak effect and/or sample heterogeneity. In the current study, linkage analysis was carried out in a sample of 62 autism-affected relative pairs with more severe obsessive-compulsive behaviors, selected from a larger (n=115) set of autism-affected relative pairs as a means of reducing sample heterogeneity. Obsessive-compulsive behaviors were assessed using the Autism Diagnostic Interview-Revised (ADI-R). In the sample with more severe obsessive-compulsive behaviors, multipoint NPL scores above 2 were observed on chromosomes 1, 4, 5, 6, 10, 11 and 19, with the strongest evidence for linkage on chromosome 1 at the marker D1S1656, where the multipoint NPL score was 3.06, and the two-point NPL score was 3.21. In follow-up analyses, analyzing the subset of families (n=35) where the patients had the most severe obsessive-compulsive behaviors generated a multipoint NPL score of 2.76, and a two-point NPL score of 2.79, indicating that the bulk of evidence for linkage was derived from the families most severely affected with obsessive-compulsive behaviors. The data suggest that there is an autism susceptibility gene on chromosome 1 and provide further support for the presence of autism susceptibility genes on chromosomes 6 and 19.
authors.affiliation: Laboratory of Molecular Neuropsychiatry, Mount Sinai School of Medicine, New York, NY 10029, USA. Joseph.Buxbaum@mssm.edu
authors.forename: J D
authors.initials: JD
authors.lastname: Buxbaum
authors.forename: J
authors.initials: J
authors.lastname: Silverman
authors.forename: M
authors.initials: M
authors.lastname: Keddache
authors.forename: C J
authors.initials: CJ
authors.lastname: Smith
authors.forename: E
authors.initials: E
authors.lastname: Hollander
authors.forename: N
authors.initials: N
authors.lastname: Ramoz
authors.forename: J G
authors.initials: JG
authors.lastname: Reichert
mesh_terms: D001321:Autistic Disorder / Q000235:genetics*; D002877:Chromosomes, Human; D002878:Chromosomes, Human, Pair 1; D002888:Chromosomes, Human, Pair 19; D002896:Chromosomes, Human, Pair 6; D005192:Family Health; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D009771:Obsessive-Compulsive Disorder / Q000235:genetics*
chemical_list: D005819:Genetic Markers