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Mapping the Genetic Landscape of Intelligence

by Muhammad Tuhin
February 2, 2025
Mapping the Genetic Landscape of Intelligence

Credit: iStock

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A groundbreaking study led by Guillaume Huguet and Thomas Renne, graduate students at the Université de Montréal (UdeM), under the guidance of medical geneticist Sébastien Jacquemont, is reshaping the understanding of how genetics influence cognitive abilities. Published in the prestigious Cell Genomics, the research delves into the significant role that copy number variation (CNV)—variations in the number of copies of certain DNA segments—plays in cognitive function, offering insights into intelligence, memory, and neurodevelopmental disorders.

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Understanding Copy Number Variation (CNV) and Cognitive Function

In typical human genetics, each individual inherits two copies of every gene, one from each parent. However, variations in the number of copies of specific genetic segments can occur, leading to deletions (loss of copies) or duplications (additional copies). Most of these CNVs do not have any noticeable impact on health. However, certain variations can have profound effects on an individual’s cognitive abilities and may be linked to various genetic conditions and neurodevelopmental disorders.

The study led by Huguet, Renne, and Jacquemont focused on the role of CNV in influencing cognitive functions such as intelligence quotient (IQ) and memory. By analyzing the CNV data from nearly 260,000 individuals in the general population, the researchers created a reference model—a “map” of CNV effects on cognition. This innovative approach not only allows for a clearer understanding of the genetic underpinnings of intelligence but also sheds light on how CNVs can impact brain function and other organs and tissues in the body.

Mapping the Genetic Impact on Cognitive Function

The researchers discovered that the type of CNV—whether it involves a deletion or a duplication—can have significantly different effects on cognitive abilities. Deletions in subcortical brain structures, where gene expression is typically strong, were linked to negative impacts on cognition. In contrast, duplications, which increase gene expression, appear to have a more profound effect when located in areas of the cortex, the part of the brain involved in complex cognitive processes such as thinking, perception, and decision-making.

More surprisingly, the study revealed that certain genetic duplications may even offer protection against neurodegenerative diseases, such as Alzheimer’s disease. Huguet explained that elderly participants with specific duplications in their genes demonstrated less cognitive decline compared to their peers. This discovery opens new possibilities for developing genetic therapies that could potentially slow or prevent cognitive degeneration in aging populations.

Expanding the Study Beyond the Brain

One of the most groundbreaking aspects of this study is its exploration of the role that CNVs in non-brain organs play in cognitive function. Although the brain has long been considered the primary organ responsible for cognitive abilities, the research uncovered how CNVs affecting other organs—previously thought to be independent from cognitive function—also contribute to cognitive outcomes.

The researchers observed that CNVs in genes expressed in organs such as the heart, liver, and kidneys were linked to cognitive abilities, suggesting that cognitive function is not solely determined by the brain. This broader perspective is particularly important in understanding comorbidities in patients with intellectual disabilities, as these individuals often experience health issues involving organs outside the brain. These findings underscore the importance of considering the entire body—not just the brain—when studying cognitive disorders and neurodevelopmental conditions.

Reimagining Neurodevelopmental Disorders and Treatment Approaches

The study represents a significant shift in how cognitive disorders and neurodevelopmental conditions are understood. By mapping the connections between CNVs, cognitive abilities, and other organs, the researchers have laid the groundwork for new diagnostic strategies. These findings could pave the way for earlier diagnoses, personalized treatments, and more effective risk management for individuals with neurodevelopmental disorders such as autism spectrum disorders.

The ability to link genetic variations to cognitive outcomes offers the potential for personalized medicine—tailoring medical care to an individual’s unique genetic profile. This approach could be transformative in neurodevelopmental medicine, allowing clinicians to predict cognitive risks based on CNV patterns, thereby providing targeted interventions before symptoms of cognitive decline or developmental delays appear.

For example, the study’s co-authors developed a prediction tool that evaluates the potential impact of CNVs on cognitive development, including how duplications and deletions might affect IQ and contribute to conditions such as autism. This tool enables clinicians to personalize their diagnostics and treatment plans by leveraging genetic data as a starting point.

Improving Early Intervention and Prevention

One of the most promising applications of this research is the ability to intervene early in children at risk for cognitive and neurodevelopmental disorders. For instance, children who carry genetic deletions that could potentially impact their cognitive function may receive early support tailored to their needs. If a child is referred to a clinic for motor-skill delays and is found to have a CNV that significantly impacts cognition, they could begin receiving appropriate therapies before cognitive symptoms emerge.

This proactive approach could prevent or reduce the severity of long-term cognitive impairments, improving the overall quality of life for children with neurodevelopmental disorders. Early intervention based on genetic profiles could also prevent the development of additional health complications, ensuring that care is more holistic and timely.

Future Implications for Personalized Neurological Medicine

While there is still much work to be done to confirm these findings and apply them in clinical practice, the study provides invaluable insights into how genetic variations influence cognitive function. The UdeM and CHU Sainte-Justine research team has opened the door to a new era of personalized neurological medicine, in which genetic data plays a central role in understanding and treating cognitive disorders.

By providing a comprehensive map of the effects of CNVs on cognition and other organs, the study offers researchers a valuable framework for future investigations. As science continues to evolve, this research could lead to new diagnostic tools, therapies, and strategies that dramatically improve the quality of life for individuals with neurodevelopmental and cognitive disorders.

Conclusion

The findings from this study represent a significant breakthrough in the understanding of how genetics influence cognitive abilities and neurodevelopmental disorders. The discovery that CNVs affecting not just the brain, but other organs, can influence cognitive outcomes offers a new perspective on how the body and brain are interconnected in determining cognitive function.

This research provides promising avenues for early diagnosis, personalized treatments, and better risk management for individuals with genetic predispositions to cognitive impairments. By taking a more holistic approach to the study of cognition, the findings suggest that the entire body, not just the brain, plays a crucial role in cognitive function.

Ultimately, this study lays the groundwork for future research that could revolutionize the diagnosis and treatment of neurodevelopmental and cognitive disorders, offering new hope for patients and their families. With these innovative insights, the future of personalized neurological medicine looks brighter than ever.

Reference: Guillaume Huguet et al, Effects of gene dosage on cognitive ability: A function-based association study across brain and non-brain processes, Cell Genomics (2024). DOI: 10.1016/j.xgen.2024.100721

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