1. ¹Department of Human Genetics, The University of Chicago, Chicago, IL, USA
2. ²Committee on Genetics, The University of Chicago, Chicago, IL, USA
3. ³Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA
4. ⁴Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA
5. ⁵Center for Molecular Neuroscience and Vanderbilt Kennedy Center, Vanderbilt University, Nashville, TN, USA

Correspondence: Dr JS Sutcliffe, Department of Molecular Physiology and Biophysics, Center for Molecular Neuroscience, 702 Light Hall, Vanderbilt University, Nashville, TN 37232-0615, USA. Tel/Fax: +1 615 936 3626; E-mail: james.s.sutcliffe@vanderbilt.edu

⁶Current address: Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

Received 20 January 2006; Revised 28 March 2006; Accepted 4 April 2006; Published online 17 May 2006.

Abstract

Autism is a pervasive developmental disorder affecting more males than females. Heritability estimates for autism can rise above 90%, and genes influencing the serotonin system are strong candidates for autism susceptibility genes, as drugs selectively acting on the serotonin system are some of the most effective treatments for maladaptive behaviors seen in autism. ITGB3 was recently identified as a male quantitative trait locus (QTL) for whole-blood serotonin levels in the Hutterites (P=0.0003). Here, we demonstrate associations between variation in ITGB3 and serotonin levels in two outbred samples (P=0.010 and 0.015). Lastly, we show that a coding variant of ITGB3 is associated with autism susceptibility in a large multiplex sample (P=0.00082), and that this variation has different effects in males and females (P=0.0018).