A Genomewide Screen of 345 Families
for Autism-Susceptibility Loci

Yonan A, Alarcon M, Cheng R, Magnusson P, Spence S, Palmer A, Grunn A, Jio, S, Terwilliger J, Liu J, Cantor R, Geschwind D, Gilliam C.
Departments of Genetics and Development, Psychiatry, and Epidemiology and Columbia Genome Center, Columbia University, and New York State Psychiatric Institute, New York; Center for Neurobehavioral Genetics and Neuropsychiatric Research Institute, Program in Neurogenetics and Departments of Neurology Human Genetics and David Geffen School of Medicine, University of California, Los Angeles

Abstract: Am J Hum Genet 2003 73(4):886-897

Findings

Dr. Yonan and her colleagues previously reported results from a scan of the human genome to identify autism susceptibility genes in 110 multiplex families. In this study they had found significant evidence for linkage to autism-spectrum disorders (ASD) on chromosomes 5, 8, 16, 19, and the X chromosome. In this follow-up study, they increased the sample size to 345 multiplex families, each with at least two siblings affected with autism or ASD. Using a measure of linkages called “multipoint maximum LOD scores”, Dr. Yonan found suggestive LOD scores on chromosomes 17, 5, 11, 4, and 8. The two largest peaks were found in both chromosome 17 near the serotonin transporter, and in chromosome 5. The serotonin marker finding is significant because many studies have shown elevated blood serotonin levels in both individuals with autism and their unaffected first-degree relatives; in addition, drugs that target the serotonin transporter can reduce autism-related symptoms. Thus, there appears to be an association with the serotonin transporter region and autism.

Conclusions

This study is the largest linkage study of autism and autism spectrum disorders carried out so far. It revealed five chromosomal regions of potential interest. However, in no single region, the generally accepted LOD score threshold of 3.0 was reached. The team of Yonan and colleagues will further investigate the most promising regions on chromosomes 5 and 17. . For the field in general the authors suggest a dramatic increase in sample size may be required to find susceptibility genes for autism. Such an increase in sample size will go beyond the capabilities of any single research group and can be achieved only through large collaborative studies by pooling families and perform dense genotyping. However, even such a large study may fail to detect linkage or association.