Gene Study Sheds Light on Women’s Lower Autism Risk

WHO:

Nature - Researchers at Boston Children’s Hospital studied autism-linked genes using human cell models.

News-Medical - Senior study author Christopher Walsh, MD, PhD, is chief of the Division of Genetics and Genomics and an Investigator of the Howard Hughes Medical Institute.

News-Medical - Lead authors Rebecca Andersen, PhD, and Maya Talukdar, PhD, worked with Walsh and colleagues on the study.

News-Medical - The research was supported by Autism Speaks, the National Institutes of Health, the Simons Foundation Autism Research Initiative, the Howard Hughes Medical Institute, Autism BrainNet, the Yang Tan Collective at Harvard University, and the Hock E. Tan and K. Lisa Yang Center for Autism Research at Harvard University.

WHAT:

Nature - Researchers reported “transcriptomic convergence”: reducing the activity of one autism-associated gene can alter the expression of many other genes, including autism-related genes.

News-Medical - Andersen said, “if you down-regulate one autism gene, you down-regulate a whole bunch of them.”

News-Medical - The researchers identified ZFX as a potential contributor to the female protective effect in autism.

News-Medical - Autism is described as four to five times more common in males than females.

Nature - The study’s organoid experiments used cerebral organoids derived from human induced pluripotent stem cells; single-cell RNA sequencing was performed on samples collected from 10 organoids at one month, 14 at two months, and 8 in an acute-knockdown group.

News-Medical - Walsh called the key messages “the idea of this transcriptomic convergence in autism” and “our identification of the ZFX gene as a potential driver of autism’s male bias.”

WHERE:

News-Medical - The research was conducted by investigators at Boston Children’s Hospital.

Nature - Human cell-culture work followed protocols approved by the Boston Children’s Hospital Institutional Review Board.

WHY:

News-Medical - The study examined how different mutations in one or more of hundreds of autism-linked genes can lead to similar conditions.

News-Medical - Researchers investigated whether X-chromosome biology could help explain females’ relative protection from severe autism symptoms.

News-Medical - The article says more than 60 X-chromosome genes escape X-chromosome inactivation; ZFX is among them.

HOW:

Nature - Researchers used CasRx and gene-targeting guide RNAs to reduce targeted transcripts, then assessed gene expression in neural progenitor cells and cerebral organoids.

Nature - The study used RNA sequencing, differential-expression analysis, and gene-regulatory-network analyses to examine the effects of gene knockdown.

News-Medical - Females typically have one X chromosome largely inactivated in each cell; ZFX escapes this inactivation and is expressed from both X chromosomes, resulting in higher ZFX expression in females.

News-Medical - Researchers found that ZFX regulates many autism-related genes; the article says increasing ZFX in males might provide partial protection, while raising ZFX levels could also benefit girls.

(UPDATED November 5, 2026 16:03 UTC)

Boston Children’s Hospital researchers found that suppressing one autism-linked gene can alter many others. They also identified ZFX, an X-chromosome gene, as a possible contributor to autism’s male bias. ZFX regulates autism-related genes, offering clues to why autism is more common in males.