Researchers have made an important breakthrough with a new study highlighting a genetic variant linked to intelligence and educational performance. This finding paves the way for better diagnostics for intellectual disabilities and opens potential treatment options.
Researchers from the Icahn School of Medicine at Mount Sinai have released a crucial study in Nature Genetics, focusing on a new genetic variant related to intellectual capabilities and educational success. This revelation enhances our understanding of diagnosing intellectual disabilities and suggests new therapeutic possibilities.
The study indicates that tandem repeats—DNA sequences where a nucleotide pattern is repeated multiple times along a chromosome—play a significant role in intellectual performance.
“The genome is filled with numerous tandem repeats that, when elongated, can interfere with the functionality of genes,” stated Andrew Sharp, PhD, Professor of Genetics and Genomic Sciences at Icahn Mount Sinai and the lead researcher. “Our work highlights how these often-overlooked genetic elements can significantly influence human intelligence.”
You can think of tandem repeats like sentences in the book of the human genome that are reiterated many times. An excessive number of these repeats can cause disruptions in genetic instructions, affecting a person’s development and cognitive skills, according to the researchers.
Employing advanced techniques such as DNA methylation profiling and genotyping, the team discovered an expansion of a specific nucleotide sequence, which is a sequence of guanine (G) and cytosine (C) bases followed by another cytosine base (GCC), within the AFF3 gene—known to be linked to educational achievement. This finding could account for about 0.3 percent of cases of intellectual disability, thereby enhancing the accuracy of genetic testing and diagnostics.
The study utilized a phenome-wide association method connecting genetic variants with human traits, emphasizing the far-reaching effects of these genetic variations on public health. “Recognizing the AFF3 expansion as a factor in intellectual disability is a step forward in achieving more accurate and prompt diagnoses,” remarked Dr. Sharp.
Future research is anticipated to expand on these initial discoveries. While this study focuses on a limited set of tandem repeat expansions, the human genome houses numerous others, many of which could be involved in various diseases, explained Dr. Sharp. The research team aims to investigate more of these repeat expansions to enhance our understanding of their distribution and influence on the human population.
Financial support for this research was provided by various grants from the National Institutes of Health (NIH): AG075051, NS105781, HD103782, and NS120241; NIH National Heart, Lung, and Blood Institute Fellowship 5120339; the Prinses Beatrix Spierfonds (W.OR20-08); the European Research Council under the EU’s Horizon 202 research and innovation program (grant 772376 — EScORIAL); UK Research and Innovation (MR/S006753/1); Barts Charity (MGU0569); and a Medical Research Council Clinician Scientist Award (MR/S006753/1).
Competing Interest Statement Pacific Biosciences contributed research support for the HiFi sequencing conducted in this study. Authors Egor Dolzhenko and Tom Mokveld are both employees and shareholders of Pacific Biosciences.
