Published: 30-10-2014 14:54 | Updated: 30-10-2014 14:57

Genetic differences provide many hints at causes of autism

Small differences in as many as a thousand genes contribute to an increased risk for autism, according to a new study from the Autism Sequencing Consortium in which researchers at Karolinska Institutet have participated. The findings are being published in the journal Nature.

The current study examined data on several types of rare, genetic differences in more than 14,000 DNA samples from parents, affected children, and unrelated individuals – by far the largest number to date – to dramatically expand the list of genes identified with autism spectrum disorder (ASD). Most of the genes that contribute to autism remain unknown, but this study increases the number of definitive autism genes almost fourfold to 33, compared to the 9 genes most closely tied to risk in recent years by similar studies in several labs. It also identified more than 70 additional, likely ASD genes. Each of these genes is mutated in more than 5 percent of individuals with autism, signifying a large, relative contribution to risk for a complex genetic disease.

For the first time, the study authors were also able to assess the effects of both inherited genetic differences and those that happen spontaneously in the sperm and eggs that go on to form human embryos. While small, rare genetic differences in the top 107 genes were found to confer a relatively large jump in a person’s risk, many more changes in other genes add smaller amounts of risk.

Interplay between gene variations

According to the authors, the interplay between gene variations, both common and rare, holds the key to understanding autism. Along these lines, the team, by looking at how many times variations occurred in each of the 107 genes, was able to predict that small differences in about 1,000 genes will eventually be found to increase autism risk.

The Autism Sequencing Consortium is an international group of scientists who share ASD samples and genetic data. All shared data and analysis is hosted by Mount Sinai Health System in New York, U.S.A. on a supercomputer called Minerva designed by Mount Sinai faculty, which enables joint analysis of large-scale data from many groups. The consortium is funded by the National Institute of Mental Health (NIMH), and the National Human Genome Research Institute (NHGRI).

Senior author of the current study in Nature is Joseph D. Buxbaum, Professor at the Icahn School of Medicine at Mount Sinai and Director of the Seaver Autism Center, together with Mark J. Daly, PhD, co-director of the Program in Medical and Population Genetics at the Broad Institute of MIT and Harvard. The Swedish part of the study was supervised by Christina Hultman, Professor at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet.


Synaptic, transcriptional, and chromatin genes disrupted in autism
Silvia De Rubeis, Xin He, Arthur P. Goldberg et al.
Nature, online 29 October 201, doi:10.1038/nature13772