The broad spectrum of autism depends on a range of genetic factors

Summary: Genetic factors affect the severity of symptoms in children on the autism spectrum, and different genetic factors are associated with different symptoms of ASD.

A source: UCSD

Autism Spectrum Disorder (ASD) is called “spectrum” because the clinical symptoms of ASD range from mild social disorders in some people to severe mental disorders or epilepsy in others.

Genetic research has offered advice on identifying genes associated with ASD, but despite finding many pieces of the puzzle, scientists still do not understand how they all fit together and why there are so many variations in ASD symptoms.

In a new study published online on June 2, 2022 Natural geneticsAn international team of scientists led by researchers from the University of California, San Diego School of Medicine, has made significant progress in understanding how the combined effects of rare mutations and general genetic variation can help a child develop or develop ASD.

“We know that the genetics of autism are complex, but we didn’t really have a picture of how rare and common variants work in genetic hereditary families,” said Jonathan Sebat, Ph.D., professor and chief specialist, author of the study. BAS Center for Molecular Genomics of Neuropsychiatric Diseases at UC San Diego School of Medicine.

In a recent study, Sebat’s team analyzed the genomes of 37,375 people in 11,213 families, at least one of whom (a child or parent) was diagnosed with ASD. The aim was to determine how a combination of genetic factors contributes to risk and clinical symptoms.

Researchers looked at a variety of factors, such as de-novo mutations, which are new genetic changes that first appear in a child; rare variants inherited from parents; and polygenic scores that quantify the genetic load of common variants of the small effect.

“When you combine all the key factors we can identify in the genome,” Sebat said, “the estimated value of DNA sequencing is twice as high as when testing the same category. Combining rare gene mutations with polygenic scores will increase the accuracy of genetic testing.”

Sex is another major factor in the risk of autism. Men were diagnosed with ASD at a ratio of 4 and 1 compared to women. In a new study, the authors found that the lower prevalence of ASD in women was partly due to a “women’s protective effect,” in which women were more resistant to genetic risk than men.

They found that the overall genetic burden was on average higher in women than in men with ASD and in their normally developing siblings than in men.

“Both the rare variants and the polygenic scores indicate evidence of a ‘female protective effect,'” Sebat said.

Researchers also looked at the effects of genetic factors on behavior, including social interactions, repetitive behaviors, and motor coordination. They found that genetic factors influenced the severity of symptoms in children with ASD and their normally developing siblings and parents.

They found that genetic factors influenced the severity of symptoms in children with ASD and their normally developing siblings and parents. Image in public domain

They also found that different factors are associated with different symptoms. Rare variants and polygenic scores affected social communication, but only rare variants affected movement coordination.

“The spectrum of severity of symptoms in ASD depends on the spectrum of genetic risk,” Sebat said. “People who meet the diagnostic criteria for autism may be on one side, but we all have different levels of risk factors. We are all on the same continent. “

Finally, the authors found that different genetic factors have different patterns of gene expression in the developing brain.

Genes associated with rare variants are strongly enriched in neurons in the fetal brain. However, genes associated with common variants are more widely represented and are not sharply enriched in specific cell types. These differences in brain expression may partially explain their association with different qualities.

According to the authors, different parts of the autism spectrum belong to each individual with its own unique combination of genetic factors.

News about genetics and autism research

Author: Scott La Fi
A source: UCSD
The connection: Scott LaFie – UCSD
Photo: Image in public domain

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Original study: Closed access.
“The phenotypic spectrum of autism is related to the combined effects of rare variants, polygenic risk, and gender,” Danny Antaki et al. Natural genetics


The phenotypic spectrum of autism is related to the combined effects of rare variants, polygenic risk, and gender.

The genetic etiology of autism spectrum disorder (ASD) is multifactorial, but it is unclear how the combination of genetic factors determines the risk.

In the large family model, we have shown that the genetic burdens of rare and polygenic risk are inversely correlated in women when they meet a gender-differentiated threshold of responsibility, and are greater in women than in men.

Recurrent mutations (DNMs), rare hereditary variants, and polygenic scores are associated with varying degrees of symptom severity in children and parents.

The effect of parental age on the risk of ASD in offspring was associated with a combination of genetic mechanisms, including DNMs accumulated in the paternal lineage and hereditary risk influencing parental behavior.

Genes associated with rare variants are richer in irritating and inhibitory neurons than genes associated with common variants.

Our results show that the phenotypic spectrum of ASD belongs to the spectrum of genetic factors influencing various neuronal development processes.

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