Summary: New research suggests that the Y chromosome may be responsible for the higher prevalence of autism in males, shifting focus away from protective factors on the X chromosome. Analyzing genetic data, researchers found that individuals with an additional Y chromosome were twice as likely to have an autism diagnosis, while an extra X chromosome had no effect on autism risk.
This discovery highlights the Y chromosome as a potential risk factor for autism, providing a new direction for research. Further studies are needed to identify the specific elements on the Y chromosome that increase autism risk.
Key Facts:
- Individuals with an extra Y chromosome are twice as likely to have autism.
- Extra X chromosomes do not increase autism risk, contradicting earlier theories.
- Findings suggest the Y chromosome plays a role in autism’s prevalence among males.
Source: Geisinger Health System
Increased risk for autism appears to be linked to the Y chromosome, a Geisinger Health System study has found, offering a new explanation for the greater prevalence of autism in males.
The results are published in Nature Communications.
Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by impaired social interaction and communication, and restricted and repetitive patterns of behavior, interests and activities. ASD is nearly four times more prevalent among males than females, but the reason for this disparity is not well understood.
One common hypothesis involves the difference in sex chromosomes between males and females—typical females have two X chromosomes, while typical males have one X and one Y chromosome.
“A leading theory in the field is that protective factors of the X chromosome lower autism risk in females,” said Matthew Oetjens, Ph.D., assistant professor at Geisinger’s Autism & Developmental Medicine Institute.
The Geisinger research team, led by Dr. Oetjens and Alexander Berry, Ph.D., staff scientist, sought to determine the effects of the X and Y chromosomes on autism risk by examining ASD diagnoses in people with an abnormal number of X or Y chromosomes, a genetic condition known as sex chromosome aneuploidy.
The team analyzed genetic and ASD diagnosis data on 177,416 patients enrolled in the Simons Foundation Powering Autism Research (SPARK) study and Geisinger’s MyCode Community Health Initiative.
They found that individuals with an additional X chromosome had no change in ASD risk, but that those with an additional Y chromosome were twice as likely to have an ASD diagnosis. This suggests a risk factor associated with the Y chromosome instead of a protective factor associated with the X chromosome.
“While these may seem like two sides of the same coin, our results encourage us to look for autism risk factors on the Y chromosome instead of limiting our search to protective factors on the X chromosome,” Dr. Berry said. “However, further research is needed to identify the specific risk factor associated with the Y chromosome.”
This analysis also confirms prior work by showing that the loss of an X or Y chromosome, known as Turner syndrome, is associated with a large increase in ASD risk. Further research is needed to determine whether the ASD risk factors associated with sex chromosome aneuploidy explain the sex difference in ASD prevalence.
About this genetics and autism research news
Author: Matthew Oetjens
Source: Geisinger Health System
Contact: Matthew Oetjens – Geisinger Health System
Image: The image is credited to Neuroscience News
Original Research: Open access.
“A genome-first study of sex chromosome aneuploidies provides evidence of Y chromosome dosage effects on autism risk” by Matthew Oetjens et al. Nature Communications
Abstract
A genome-first study of sex chromosome aneuploidies provides evidence of Y chromosome dosage effects on autism risk
A female protective effect has long been postulated as the primary explanation for the four-fold increase of autism spectrum disorder (ASD) diagnoses in males versus females. However, genetic and epidemiological investigations of this hypothesis have so far failed to explain the large difference in ASD prevalence between the sexes.
To address this knowledge gap, we examined sex chromosome aneuploidy in a large ASD case-control cohort to evaluate the relationship between X and Y chromosome dosage and ASD risk.
From these data, we modeled three relationships between sex chromosome dosage and ASD risk: the extra Y effect, the extra X effect, and sex chromosome haploinsufficiency.
We found that the extra Y effect increased ASD risk significantly more than the extra X effect.
Among females, we observed a large association between 45, X and ASD, confirming sex chromosome haploinsufficiency as a strong ASD risk factor.
These results provide a framework for understanding the relationship between X and Y chromosome dosage on ASD, which may inform future research investigating genomic contributors to the observed sex difference.
