1. ¹Laboratory of Molecular Neuropsychiatry, Mount Sinai School of Medicine, New York, NY, USA
2. ²Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA
3. ³Department of Neurobiology, Mount Sinai School of Medicine, New York, NY, USA
4. ⁴Seaver Autism Research Center, Mount Sinai School of Medicine, New York, NY, USA

Correspondence: JD Buxbaum, Laboratory of Molecular Neuropsychiatry, Department of Psychiatry, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1668, New York, NY 10029, USA. E-mail: Joseph.Buxbaum@mssm.edu

Current affiliation for M Keddache: Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

Received 28 March 2003; Revised 23 September 2003; Accepted 6 October 2003; Published online 23 December 2003.

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.