October 20, 2021

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by: admin

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Tags: Autismlinked, decrease, Genetic, Increase, Intelligence, Spectrum, variants

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Categories: autism

Autism-linked genetic variants enhance, lower intelligence | Spectrum

Common and rare variants in or near certain autism-associated genes can have opposite effects on cognition. Likewise, some autistic people carry autism-related variants with opposing effects on levels of intelligence.

Two independent teams presented the unpublished results yesterday at the American Society of Human Genetics 2021 conference, which is being held virtually for the second year in a row.

Previous research shows that a mix of common and rare variants work together to affect a person’s likelihood of having autism. Common variations that have subtle effects on a person’s characteristics tend to be associated with high intelligence quotient (IQ). Rare variants, on the other hand, have stronger effects and typically have a below-average IQ. However, it was unclear how variants that contribute to the same disorder could have such different effects on cognition.

Solving this mystery could help researchers better understand the genetic basis of the wide variety of traits in autistic people, says Daniel Weiner, a graduate student in Elise Robinson’s lab at the Broad Institute in Boston, Massachusetts, who presented some of the work.

“This type of approach is a way of thinking about how convergence of more common and less common variations in autism can occur,” says Weiner.

Opposing effects:

Weiner and his colleagues analyzed the entire genome sequences of 5,048 people with autism and their parents, all of whom participate in the Simons Simplex Collection (SSC) and Simons Powering Autism Research for Knowledge (SPARK). Both projects are funded by the Simons Foundation, Spectrum’s parent organization. The researchers also separately analyzed the sequences of 4,334 autistic people and their parents from the Psychiatric Genomics Consortium (PGC), a study of 11 neurological and psychiatric disorders, including autism, based at the University of North Carolina at Chapel Hill.

They looked for common variants associated with high levels of education – a proxy for high IQ – in and near 255 genes associated with autism; rare mutations with loss of function in these genes are known to be associated with low IQ. They used a statistical method they had developed a few years ago, called the polygenic transmission imbalance test, to determine the extent to which the autistic children had inherited these common variants.

On average, autistic children inherit more IQ-enhancing variants in or near autism-related genes than one might expect, analysis shows, and this pattern holds true for both the Simons and PGC sequences.

“Even with those genes that have a disorder with a decreased IQ in [autism], on average we still see an over-transfer of the IQ-increasing risk for frequent variants, ”says Weiner.

Separate ways:

In a separate analysis, another team compared the sequences of 6,929 autistic people and 32,663 non-autistic people with similar IQs; the data came from the SSC and SPARK cohorts and four others.

Autistic people were more likely than their non-autistic peers to have large, rare mutations that lower IQ, the team found. They also had more common variants that increase IQ.

Taking into account the differences in the number of intelligence-associated common variants did not shift the impact of the large mutations on a person’s likelihood of having autism, the study shows.

“Importantly, these results suggest that these two genetic factors can independently increase the risk of autism,” said Zoe Schmilovich, a PhD student in Guy Rouleau’s laboratory at McGill University in Montreal, Canada, at the presentation of the work.

The two analyzes taken together suggest that different biological pathways that underpin differences in cognition may contribute to autism, Weiner says.

Read more reports from the American Society of Human Genetics’ annual 2021 meeting.

Quote this article: https://doi.org/10.53053/WCXO7531

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