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VANDERBILT MEDICINE :: WINTER 2014
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Autism: Piecing Together the Genetic Puzzle


By Leigh MacMillan
January 2010

A multi-center team, including investigators in Vanderbilt’s Center for Human Genetics Research, has identified the first common genetic variation associated with autism.

The findings, reported in Nature and in the Annals of Human Genetics, point to a particular spot in the genome that may increase a person’s risk for the neurodevelopmental disorder and suggest the involvement of molecules that form connections between brain cells.

Autism is characterized by impaired verbal communication and social interaction, and by restricted and repetitive patterns of interest or behavior. It is part of a spectrum of disorders (ASD) that can range from relatively mild to quite severe and affect as many as one in 150 children in the United States, about three-quarters of them boys.

Evidence from twin and sibling studies has demonstrated that autism has a strong genetic component, but despite many attempts to find genetic risk factors, “there is no consensus on the underlying genetic architecture of the disorder,” said Jonathan Haines, Ph.D., director of the Vanderbilt Center
for Human Genetics Research (CHGR) and a co-author of both studies.

Haines and longtime collaborator Margaret Pericak-Vance, Ph.D., director of the Miami Institute for Human Genomics at the University of Miami, conducted a genome-wide association study (GWAS) to search for common genetic variation that increases susceptibility for ASD. Common genetic variants are spots in the genome where a variable letter of the DNA code – called an SNP (single nucleotide polymorphism) – is present in at least 5 percent of the population.

The researchers examined 1 million SNPs in a discovery dataset that included 1,390 individuals from 438 autistic Caucasian families. They identified 96 SNPs as being strongly associated with autism risk. Using an independent validation dataset of 2,390 individuals from 457 autistic families, and analysis of 550,000 genetic markers, the investigators narrowed the list of potential autism risk SNPs. Two of the top 96 SNPs resided in a region on chromosome 5p14.1, which the researchers examined more closely, finding eight SNPs that associated with autism in this region.

Investigators at the Children’s Hospital of Philadelphia performed a GWAS on two additional datasets (one 780 family-based group and one case-control group with 1,204 cases and 6,491 controls). James Sutcliffe, Ph.D., a CHGR investigator and co-author of the Nature paper, provided additional Vanderbilt samples to the Philadelphia group.

That analysis also identified the 5p14.1 chromosomal region as containing common genetic variants associated with ASD.

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