International research teams have clarified how genetic risk for autism spectrum disorders (ASD) relates to autism-like traits across the general population, according to a new collaborative study involving the University of Bristol, the Broad Institute of Harvard and MIT, and Massachusetts General Hospital (MGH).
The study examined whether genetic factors associated with clinically diagnosed ASD also influence social, communication and behavioural traits in people who do not carry an ASD diagnosis. Published in Nature Genetics, the findings show that the same types of inherited and de novo genetic influences linked to ASD contribute to a spectrum of developmental and behavioural variation in the wider population. Individuals diagnosed with ASD appear to represent the extreme end of this continuum.
Autism spectrum disorders affect roughly 1 in 100 children and are defined by challenges in social interaction, differences in communication and language, and repetitive or restricted behaviours. These core features can be present to varying degrees among people without an ASD diagnosis, forming what researchers describe as an underlying behavioural continuum.
Advances in genome sequencing and large-scale genetic analysis have revealed a more detailed picture of ASD genetics. Much of ASD risk stems from polygenic influences — the combined effect of thousands of common genetic variants each contributing a small amount to overall risk. In addition, some cases involve rare variants of large effect that often arise de novo, meaning they are not inherited from either parent.
“Until recently the evidence was indirect, but with measurable genetic signals — both polygenic risk scores and identified de novo mutations — we can now show clearly that genetic factors that increase autism risk are present throughout the population and influence social communication and behaviour,” said Dr Mark Daly, co-director of the Broad Institute’s Medical and Population Genetics Program and a senior author on the paper.
Co-first author Dr Elise Robinson of MGH added that combining behavioural and cognitive data from the general population with genetic data makes it possible to untangle how different types of genetic risk act. “This approach gives us clearer expectations about which disorders or traits may be associated with specific categories of genetic risk,” she said.
Study co-first author Dr Beate St Pourcain (Medical Research Council Integrative Epidemiology Unit, University of Bristol, and Max Planck Institute for Psycholinguistics) emphasised the value of collecting rich phenotypic and genetic information in typically developing children. “Such data improve how we design and interpret studies of complex neurodevelopmental and psychiatric disorders,” she said.
The research combined data from multiple sources. Population-based data came from the Avon Longitudinal Study of Parents and Children (ALSPAC), a long-running Bristol-based cohort. Family-based data included the Simons Simplex Collection (SSC), which pairs ASD cases with unaffected siblings. Large ASD data sets were contributed by major international studies and consortia, including the Psychiatric Genomics Consortium autism group, the Danish iPSYCH autism project, the SSC itself, and the Autism Sequencing Consortium.
Professor George Davey Smith, co-author and scientific director of ALSPAC, noted that many health-related traits display a continuum of risk shaped by common and rare genetic variation as well as environmental and chance factors. “This study shows that the same continuum concept applies to a condition often seen as binary — you either have ASD or you do not — by demonstrating how genetic risk maps onto a broad range of social and communication traits,” he said.
By demonstrating overlapping genetic influences between diagnosed ASD and autistic-like traits in the general population, the study suggests several practical pathways for future research. First, behavioural measures in typically developing children can act as proxies to identify biological pathways relevant to ASD. Second, differentiating the impacts of polygenic background versus rare de novo variants can guide expectations about associated cognitive and developmental profiles. Third, the approach used in this work can be extended to other neuropsychiatric conditions, such as schizophrenia, to explore how genetic risk relates to subtler, population-level traits.
Overall, the results support a model in which autism-related genetic variation is widely distributed across people, shaping a range of behaviours and developmental outcomes. Clinical ASD represents one end of this distribution, where genetic and possibly environmental factors combine to produce more pronounced impairment. Using population cohorts alongside clinical collections improves our ability to trace how specific genetic influences translate into observable developmental differences.
Source: University of Bristol
Image source: Adapted from the University of Bristol press release.
Original research: Robinson EB, St. Pourcain B et al., “Genetic risk for autism spectrum disorders and neuropsychiatric variation in the general population,” Nature Genetics (paper published during the week of March 21, 2016).