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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

Molecular Psychiatry volume 9, pages 144–150 (2004)Cite this article

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.

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Acknowledgements

This work was supported by the Seaver Autism Research Center and Cure Autism Now, as well as by the National Institute of Mental Health through a STAART grant (U54 MH 066673). We thank AGRE and Dr T Conrad Gilliam for the genotyping data, all of which were performed in the laboratory of Dr Gilliam and can be found on the AGRE website (www.agre.org).

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Author notes

  1. M Keddache

    Present address: Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA

Authors and Affiliations

  1. Laboratory of Molecular Neuropsychiatry, Mount Sinai School of Medicine, New York, NY, USA

    J D Buxbaum, M Keddache, N Ramoz & J G Reichert

  2. Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA

    J D Buxbaum, J Silverman, M Keddache, C J Smith, E Hollander, N Ramoz & J G Reichert

  3. Department of Neurobiology, Mount Sinai School of Medicine, New York, NY, USA

    J D Buxbaum

  4. Seaver Autism Research Center, Mount Sinai School of Medicine, New York, NY, USA

    J D Buxbaum, J Silverman, M Keddache, C J Smith, E Hollander, N Ramoz & J G Reichert

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Correspondence to J D Buxbaum.

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Buxbaum, J., Silverman, J., Keddache, M. et al. 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. Mol Psychiatry 9, 144–150 (2004). https://doi.org/10.1038/sj.mp.4001465

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