Source: NHGRI

Five novel genetic variants have been linked to autism spectrum disorders (ASD), according to a new study. The research, released as a preprint by biorxiv.org last week, involved a genome-wide association study of more than 46,000 people and marks the first time that individual variants have been linked to the conditions. Some significant variants were also found to be linked to other neurological disorders, such as schizophrenia.

ASD is generally considered to be a collection of heritable, heterogeneous neurodevelopmental phenotypes. The broadness of conditions covered by the classification contributes to the fact that, at present, autism spectrum disorders are thought to be diagnosed in more than 1% of the population. Despite the prevalence of ASD, however, previous studies have been unable to identify genomic variants that could explain the highly heritable nature of the conditions.

“While early GWAS permitted estimates that common polygenic variation should explain a substantial fraction of the heritability of ASD, individually significant loci remained elusive,” the authors wrote. “This was suspected to be due to limited sample size since studies of schizophrenia – with similar prevalence, heritability, and reduced fitness – and major depression achieved striking results only when sample sizes five to ten times larger than available in ASD were employed. This study has finally borne out that expectation with definitively demonstrated significant “hits”.”

To try to identify individual variants linked to ASD, the research team analysed genetic data from more than 46,000 participants of a Danish population genomic resource. The sample included 18,381 participants with an autism spectrum disorder and 27,969 control cases, where ASD had not been diagnosed. Through a novel approach to data analysis, called MTAG, the team were able to identify 5 genomic variants which displayed genome-wide significant association with ASD.

In further work, they also compared the genomic data of ASD participants with that of previously-acquired information about patients with schizophrenia and major depression. This comparison allowed them to identify another 7 genomic variants which were shared by the different neurological conditions at significant levels.

Not only could this work help us to improve our understanding of autism spectrum disorders, it also demonstrates that large genome-wide association studies are an effective avenue for studying these types of conditions. The team hope that their work will encourage similar research by other groups.

The authors concluded, “We have established a first compelling set of common variant associations in ASD and have begun laying the groundwork through which the biology of ASD and related phenotypes will inevitably be better articulated.”