X chromosome exerts additional affect on mind growth | Spectrum
X-tra effects: Brain regions with an overly large influence of the X chromosome (yellow) support functions such as attention, decision-making as well as sensory and motor skills.
The X chromosome has a more than expected genetic influence on the structure of several brain regions, a new study shows. The X-linked genes that may underlie this oversized influence have links to autism and intellectual disability.
“There have already been indications that the X chromosome is likely suspicious because it is involved with the brain,” says lead researcher Armin Raznahan, head of the developmental neurogenomics department at the US National Institute of Mental Health. For example, many X chromosome genes – including those that underlie several autism-related disorders such as fragile X syndrome and Rett syndrome – are expressed in the brain.
However, the new evidence suggests that although the X chromosome contains only 5 percent of the human genome, it plays a privileged role in shaping the brain – one that could be particularly relevant to developmental conditions. In addition, this influence can be stronger in men than in women, the study shows.
“What they show is that X is fundamentally different,” says David Glahn, a professor of psychology at Harvard University who was not involved in the new study. “It’s out of scale.”
Research over the past decade has linked genetic variations to changes in brain function, such as overall size or connectivity patterns between regions, says Glahn. But “the X chromosome and the Y chromosome are fundamentally under-explored,” because their inclusion requires additional analytical legwork, he says.
Thanks to powerful data sets compiling gene sequencing and brain imaging data from tens of thousands of people, this oversight could soon fade. The new work is the latest in a series of studies to tap into the UK biobank, which contains genetic and imaging data on nearly 40,000 people.
“The ability to get into the [the] The X chromosome and influencing the brain structure was only possible when these huge data sets recently became available, ”says Neda Jahanshad, associate professor of neurology at the University of Southern California at Los Angeles, who was not involved in the study. “This is a really important first investigation into that.”
Raznahan and colleagues analyzed genetic data and magnetic resonance imaging scans from 32,256 adults, approximately half of whom are women, from the general population.
From the brain scans, the researchers determined the thickness, volume and surface area of 358 regions of each participant’s cortex. They looked for links between these structural features and optimizations in the participants’ genetic code, then calculated the proportion of variation in the cortical features associated with those on the X chromosome. Raznahan and his team published their results in Nature Neuroscience in July.
The X chromosome exerts a greater influence on the structure of several brain regions, including the prefrontal cortex, the sensorimotor cortex, and the temporoparietal junction than would be expected based on its genomic size, the researchers found. And this pattern was clearer for the surface than for the thickness or volume of a brain region. In fact, the genetic variation on the X chromosome explains more than 20 percent of the variation in surface areas of multiple regions, the study said.
The influence of the chromosome on the temporoparietal junction is especially fascinating when it comes to autism, says Glahn. The activity and development of the region is linked to the theory of the mind or the ability to discern the feelings and thoughts of others. Some autistic people find this skill challenging.
Networks that involve attention, decision-making, and sensory and motor functions overlap significantly with the areas of the brain most affected by the X chromosome variation, the researchers also found, suggesting that the X chromosome has adaptive behavior supports, says Raznahan.
“The organizational structure certainly gives a first insight,” says Jahanshad. However, an important next step is to correlate the genetic variation on the X chromosome with patterns in functional imaging data and actual behavioral traits. (Raznahan says he plans to do just that in follow-up studies.)
A separate analysis revealed 20 X-linked genes, which are associated with the surface of the brain regions, which show strong overall X-chromosome influences. Several of these genes are implicated in intellectual disability, hydrocephalus, and autism.
The work complements another UK biobank study published in the same journal in April in which a separate team examined specific X chromosome genes associated with brain features such as the integrity of nerve bundles in the brain.
The influence of the X chromosome on brain anatomy was more than twice as great in men as it was in women, as Raznahan’s team also showed. The degree of this difference in heredity between men and women correlated with the degree of gender difference in the cortical surface, which tends to be larger in men.
If the X chromosome plays a more prominent role in determining some aspects of brain structure in men than in women, as the results suggest, it may offset the fact that men only have one X while women have two.
The results add another chain of evidence to the often controversial idea that there are gender differences in the brain. However, it’s not clear how the X chromosome could affect these differences or how they relate to actual behavior, says Glahn. “The really interesting part is just asking these gender difference questions.”
Overall, the new work serves as a challenge to researchers to include the X chromosome in studying the genetic patterns of the brain, says Raznahan. “We would be happy if this work did in any way to encourage people to study the X chromosome more.”