1. ¹Geriatrics Research Education and Clinical Center, Puget Sound Veterans Affairs Medical Center, Seattle, WA, USA
2. ²Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, WA, USA
3. ³Department of Neurology, University of Washington, Seattle, WA, USA
4. ⁴Department of Pharmacology, University of Washington, Seattle, WA, USA
5. ⁵Department of Psychology and the Center on Human Development and Disability, University of Washington, Seattle, WA, USA
6. ⁶Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA
7. ⁷Department of Medicine, Division of Medical Genetics, University of Washington, Seattle, WA, USA
8. ⁸Department of Biostatistics, University of Washington, Seattle, WA, USA
9. ⁹Department of Pediatrics, University of California, Irvine, CA, USA
10. ¹⁰Department of Psychiatry, Division of Child and Adolescent Psychiatry, University of Utah, Salt Lake City, UT, USA
11. ¹¹Department of OB/GYN, University of Rochester Medical Center, Rochester, NY, USA
12. ¹²Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA

Correspondence: Dr GD Schellenberg, Veterans Affairs Medical Center (182b), 1660 S. Columbian Road, Seattle, WA 98108, USA. E-mail: zachdad@u.washington.edu

Received 28 February 2006; Revised 28 April 2006; Accepted 1 May 2006; Published online 1 August 2006.

Abstract

We performed a genome-wide linkage scan using highly polymorphic microsatellite markers. To minimize genetic heterogeneity, we focused on sibpairs meeting the strict diagnosis of autism. In our primary analyses, we observed a strong linkage signal (P=0.0006, 133.16 cM) on chromosome 7q at a location coincident with other linkage studies. When a more relaxed diagnostic criteria was used, linkage evidence at this location was weaker (P=0.01). The sample was stratified into families with only male affected subjects (MO) and families with at least one female affected subject (FC). The strongest signal unique to the MO group was on chromosome 11 (P=0.0009, 83.82 cM), and for the FC group on chromosome 4 (P=0.002, 111.41 cM). We also divided the sample into regression positive and regression negative families. The regression-positive group showed modest linkage signals on chromosomes 10 (P=0.003, 0 cM) and 14 (P=0.005, 104.2 cM). More significant peaks were seen in the regression negative group on chromosomes 3 (P=0.0002, 140.06 cM) and 4 (P=0.0005, 111.41 cM). Finally, we used language acquisition data as a quantitative trait in our linkage analysis and observed a chromosome 9 signal (149.01 cM) of P=0.00006 and an empirical P-value of 0.0008 at the same location. Our work provides strong conformation for an autism locus on 7q and suggestive evidence for several other chromosomal locations. Diagnostic specificity and detailed analysis of the autism phenotype is critical for identifying autism loci.