The genetic architecture of risk for autism spectrum disorder

May 16, 2017 by Karen Zusi, Broad Institute of MIT and Harvard
The genetic architecture of risk for autism spectrum disorder
Credit : Susanna M. Hamilton, Broad Communications

A new study of inherited genetic risk indicates that common genetic variations throughout the genome act in addition to rare, deleterious mutations in autism-associated genes to create risk for autism.

Studies of for developing (ASD) often compare DNA from those diagnosed with to that of neurotypical controls, but these approaches can be confounded by external factors. To get a clearer look at the genetic underpinnings of autism risk, a team led by researchers from the Broad Institute's Stanley Center for Psychiatric Research and the Analytic and Translational Genetics Unit at Massachusetts General Hospital and Harvard Medical School took a new approach, published in Nature Genetics, comparing genetic influences within families in which a child has been diagnosed with autism.

In the human genome, common genetic variations can each contribute a small level of risk for developing a given disorder. These variants can be aggregated to create a "polygenic risk score," which represents part of an individual's overall disorder risk.

In this study, Elise Robinson, an associated scientist at Broad and assistant professor of epidemiology at the Harvard T.H. Chan School of Public Health, first author Daniel Weiner, a scientist in Robinson's lab, and colleagues calculated polygenic risk scores for developing autism in members of 6,454 families with one or more diagnosed with ASD. The risk scores were based on the participants' individual genotypes compared against data from genome-wide association studies.

On average, children's genetic risk scores for any phenotype equal an average of their parents' scores. However, the team discovered that children with ASD have a higher risk score on average for developing ASD—meaning that more of the contributing common variants from the parents have been inherited together, versus what would be expected if the risk score was an average of the parents'. Children with ASD in the study were also likely to have independently over-inherited their parents' polygenic risk for developing schizophrenia, as well as polygenic influences associated with more years of education (which are strongly correlated with the polygenic influences on IQ score).

The independent inheritance of these influences may help to explain the different ways that autism can manifest. For example, higher polygenic risk for schizophrenia was associated with lower IQ , whereas higher polygenic scores for years of education were associated with higher IQ, in children with ASD.

The team also found that risk for developing ASD is increased beyond the common polygenic risk if a rare, harmful mutation, newly arising in the child, occurs in an autism-associated gene. In children with ASD, these rare variants are associated with more severe neurodevelopmental impacts, such as intellectual disability, seizures, and motor function delay.

The study results point to multiple types of genetic risk for ASD, highlighting the need for a better understanding of the behavioral and cognitive traits associated with autism in order to eventually develop models or therapies. Using genetic data from parents and their children to dissect the roots of a disorder also eliminates many potential confounding factors, and the research team noted the utility of this analytic method for studying other types of polygenic risk.

Explore further: Autism genes are in all of us, new research reveals

More information: Daniel J Weiner et al. Polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders, Nature Genetics (2017). DOI: 10.1038/ng.3863

Related Stories

Autism genes are in all of us, new research reveals

March 21, 2016
New light has been shed on the genetic relationship between autistic spectrum disorders (ASD) and ASD-related traits in the wider population, by a team of international researchers including academics from the University ...

Scientists herald 'tipping point' in ability to predict academic achievement from DNA

July 19, 2016
Scientists from King's College London have used a new genetic scoring technique to predict academic achievement from DNA alone. This is the strongest prediction from DNA of a behavioural measure to date.

Polygenic risk score helpful for women with familial breast CA

December 18, 2012
(HealthDay)—For women affected by familial breast cancer, a polygenic risk score based on 22 genomic variants can identify women at high-risk of breast cancer, according to a study published in the Dec. 10 issue of the ...

Adding up autism risks

October 15, 2012
The causes of autism and autism spectrum disorder (ASD) are complex, and contain elements of both nature (genes) and the environment. New research published in BioMed Central's open access journal Molecular Autism shows that ...

Gene variants implicated in ADHD identify attention and language

October 15, 2014
Are deficits in attention limited to those with attention-deficit/hyperactivity disorder (ADHD) or is there a spectrum of attention function in the general population? The answer to this question has implications for psychiatric ...

Recommended for you

New software helps detect adaptive genetic mutations

February 20, 2018
Researchers from Brown University have developed a new method for sifting through genomic data in search of genetic variants that have helped populations adapt to their environments. The technique, dubbed SWIF(r), could be ...

15 new genes identified that shape human faces

February 20, 2018
Researchers from KU Leuven (Belgium) and the universities of Pittsburgh, Stanford, and Penn State have identified 15 genes that determine facial features. The findings were published in Nature Genetics.

New algorithm can pinpoint mutations favored by natural selection in large sections of the human genome

February 20, 2018
A team of scientists has developed an algorithm that can accurately pinpoint, in large regions of the human genome, mutations favored by natural selection. The finding provides deeper insight into how evolution works, and ...

Highly mutated protein in skin cancer plays central role in skin cell renewal

February 20, 2018
Approximately once a month, our skin completely renews itself. If this highly coordinated process goes awry, it can lead to a variety of skin diseases, ranging from skin cancer to psoriasis. Cells lining such organs as skin ...

Study of smoking and genetics illuminates complexities of blood pressure

February 15, 2018
Analyzing the genetics and smoking habits of more than half a million people has shed new light on the complexities of controlling blood pressure, according to a study led by researchers at Washington University School of ...

New mutation linked to ovarian cancer can be passed down through dad

February 15, 2018
A newly identified mutation, passed down through the X-chromosome, is linked to earlier onset of ovarian cancer in women and prostate cancer in father and sons. Kunle Odunsi, Kevin H. Eng and colleagues at Roswell Park Comprehensive ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.