Research Highlights

Largest study of its kind identifies candidate autism genes

Published online 1 November 2014

Aisha El-Awady

Over 5% of autistic individuals acquire new loss-of-function mutations in some of the candidate genes
Over 5% of autistic individuals acquire new loss-of-function mutations in some of the candidate genes
© S. De Rubeis / Nature  Enlarge image

People suffering from autism spectrum disorder (ASD) show varying symptoms—the degree of impairment that develops early on in life is caused by a wide range of genetic mutations. By identifying genes likely to affect the risk of developing ASD, scientists can better understand this neurodevelopmental disorder.

An international team of researchers, led by Mark J. Daly from Harvard Medical School in Boston, Massachusetts and Joseph Buxbaum from Icahn School of Medicine at Mount Sinai in New York, and including Angel Carracedo from King Abdulaziz University in Jeddah, Saudi Arabia, studied and quantified the various types of gene mutation associated with risk for ASD, publishing their findings in Nature1.

Their study—“the largest of its kind” according to Buxbaum—identified 107 candidate genes that will likely affect the risk for autism. 

Using exome sequencing (selective sequencing of all protein-coding genes in a genome), the team studied 3,871 individuals with ASD and 9,937 controls that were either parents or unrelated controls. 

The team also found that over five per cent of autistic individuals acquire what are known as de novo (new) loss-of-function mutations in some of the candidate genes. The implicated genes encode proteins involved in the transmission of signals between nerves, proteins involved in regulating the process by which a gene sequence directs protein synthesis inside the cell, as well as proteins that modify chromatin architecture to allow regulation of gene expression.

“We identified new autism genes and biological pathways, including three important pathways involved in brain development and function,” says Buxbaum. The discoveries provide the basis for novel cell models for autism, which will help develop better medicines, he adds. 


  1. De Rubeis, S., et al. Synaptic, transcriptional and chromatin genes disrupted in autism. Nature. (2014)