Researchers analyzing brain tissue from 30 adults found over 3,000 genes show sex-based differences in expression, with 133 displaying consistent patterns across brain regions.
The study, published in Science, was led by Alex DeCasien from the National Institute on Aging and the National Institute of Mental Health.
Using single-nucleus RNA sequencing on cortical samples from 15 men and 15 women, the team focused on six brain regions known to vary in volume by sex.
Although biological sex accounts for less than 1% of global gene expression variation — as noted by Emory University neuroscientist Donna Maney — the identified genetic differences are statistically robust, and reproducible.
Most of these sex-biased genes are not located on sex chromosomes but are autosomal genes regulated by steroid hormones.
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The 133 consistently expressed genes are linked to susceptibility for neuropsychiatric and neurodegenerative disorders including ADHD, schizophrenia, depression, and Alzheimer’s disease.
These findings assist explain why prevalence rates for such conditions differ between males and females, moving beyond social or diagnostic biases to biological mechanisms.
The researchers acknowledge that some observed differences could stem from divergent life experiences or socialization, though the genetic signals remain significant.
Understanding these molecular distinctions may eventually inform sex-aware approaches to diagnosis, treatment, and prevention of brain disorders.
How many brains were studied in the research?
The study analyzed tissue samples from 30 adults, with equal representation of 15 males and 15 females.
What percentage of gene expression variation is attributed to biological sex according to the study?
Biological sex explains less than 1% of the total variation in global gene expression in the brain, as cited by neuroscientist Donna Maney.