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Study Suggests Subset of Variants Involved in Autism May Influence Population Behavioral Variation

NEW YORK (GenomeWeb) – A new study suggests that some of the same genetic variants implicated in autism spectrum disorder risk likely contribute to the range of social behaviors found across the population as a whole.

By bringing variant linkage data and summary statistics from past genome-wide association studies of ASD together with SNP association data for a population cohort with documented social and communication profiles, an international team led by investigators in the US and the UK looked for genetic correlation between the traits.

Findings from the analysis, published online today in Nature Genetics, suggested that around one-quarter of the common variants associated with ASD through past GWAS may also contribute to social behavior or communication skills in children from the general population. Likewise, the team's follow-up analyses indicated that similar overlap between de novo variants involved in ASD and behavior may exist as well, perhaps contributing to a spectrum of social, behavioral, and/or communication effects.

"These results suggest that familiality should be studied in a manner beyond a count of categorically affected family members and that trait variation in controls can provide insight into the underlying etiology of severe neurodevelopmental and psychiatric disorders," senior author Mark Daly, co-director of the Broad Institute's medical and population genetics program, and his co-authors wrote.

Although a wide range of genetic variants and de novo mutations have been associated with ASD, not much is known about the effects, if any, that subsets of these genetic features might have in the general population.

"Almost all genetic risk factors for ASDs can be found in unaffected individuals," Daly and co-authors wrote. "Across healthy populations, there is also substantial variability in capacity for social interaction and social communication. Although such phenotypic variation is well established, the genetic relationship between neuropsychiatric disorders and typical social and behavioral variation remains unclear."

With that in mind, the team set out to explore the possibility that subtle or intermediate forms of traits found in individuals with ASD, involving the same genetic variants, might contribute to differences in social behavior within the general population.

The researchers started by searching for common variants associated with ASD in thousands of samples collected by the Psychiatric Genomics Consortium ASD group that might also impact social and communication disorder checklist scores for children enrolled in a UK population cohort called the Avon Longitudinal Study of Parents and Children (ALSPAC), which includes children born in Bristol in 1991 or 1992.

Indeed, the team saw signs of genetic correlation between variants contributing to social behavior and communication deficits and those identified in more than 10,600 ASD cases and controls enrolled through the Psychiatric Genomics Consortium — genetic overlap the group verified with association data from nearly 8,000 cases and more than 11,300 controls from the Danish iPSYCH project.

From these data, the researchers estimated that around one-quarter of the common variants associated with ASD also corresponded with social behavior or communication test outcomes, on par with the estimated genetic overlap between ASD and psychiatric conditions such as schizophrenia, bipolar disorder, or major depressive disorder.

On the other hand, the team noted, roughly three-quarters of ASD-associated common variants overlapped between the Psychiatric Genomics Consortium and Danish iPSYCH projects.

Consistent with the notion that ASD-related variants may contribute to a continuum of traits with ASD at one end of the spectrum, the researchers also saw some overlap between de novo variant associations with behavioral measurements in thousands of ASD-affected children and unaffected siblings enrolled through the Simons Simplex Collection. 

Together, the study's authors explained, such findings "strongly suggest that genetic influences on ASD risk — both inherited and de novo — influence typical variation in the population in social and communication ability."