1. ¹Department of Psychiatry, University of Iowa College of Medicine, Iowa City, IA, USA
2. ²Neurodevelopmental Disorders Research Center and Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA
3. ³Department of Biostatistics, Division of Statistical Genetics, University of Iowa College of Public Health, Iowa City, IA, USA
4. ⁴Department of Pediatrics and the Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City, IA, USA
5. ⁵Department of Psychiatry, Tufts University School of Medicine, Boston, MA, USA

Correspondence: TH Wassink, MD, University of Iowa College of Medicine, Psychiatry Research/MEB, Iowa City, IA 52242, USA. E-mail: thomas-wassink@uiowa.edu

Received 9 October 2002; Revised 13 January 2003; Accepted 25 February 2003; Published online 6 April 2004.

Abstract

Impaired reciprocal social interaction is one of the core features of autism. While its determinants are complex, one biomolecular pathway that clearly influences social behavior is the arginine–vasopressin (AVP) system. The behavioral effects of AVP are mediated through the AVP receptor 1a (AVPR1a), making the AVPR1a gene a reasonable candidate for autism susceptibility. We tested the gene's contribution to autism by screening its exons in 125 independent autistic probands and genotyping two promoter polymorphisms in 65 autism affected sibling pair (ASP) families. While we found no nonconservative coding sequence changes, we did identify evidence of linkage and of linkage disequilibrium. These results were most pronounced in a subset of the ASP families with relatively less severe impairment of language. Thus, though we did not demonstrate a disease-causing variant in the coding sequence, numerous nontraditional disease-causing genetic abnormalities are known to exist that would escape detection by traditional gene screening methods. Given the emerging biological, animal model, and now genetic data, AVPR1a and genes in the AVP system remain strong candidates for involvement in autism susceptibility and deserve continued scrutiny.