Intelligence in the HTT Gene

By Daniel Walocha ‘19

Huntington's Disease.jpg
Figure 1. Huntington’s disease is caused by trinucleotide repeats in the HTT gene, which has recently been correlated to intelligence.

Huntington’s Disease is caused by a trinucleotide repeat of the HTT gene. The wild type has a repeat ranging from 10 to 35, but beyond 39 repeats causes the disease characterized by significant impairments in the basal ganglia and neurodegeneration. The CAG repeats in the HTT gene cause the production of an abnormally long Huntington protein, which impairs the function of normal Huntington protein—characterizing it as an autosomal dominant disease. However, Dr. Jessica Lee et al. from the University of Michigan, have shown that the CAG nucleotide repeats are also correlated with general intelligence.

Previous studies have shown that the repeats lead to abnormal neurological development. This development creates circuits that are abnormal in the brain, but are functional early on due to compensatory mechanisms and the late onset of the disease. Children with repeats that range from 15-58 were studied for cognitive abilities, motor skills, and behavior longitudinally. CAG repeats can also indicate the onset age of the disease, so the sample studied was controlled to exclude kids at high risk for early onset. A number of tests were administered to test intelligence, including the Wechsler Intelligence Scale for Children. With a p < 0.006, the pattern of intelligence follows an inverted “U” shape, with 40-41 repeats exhibiting the highest intelligence. On either side of this peak, intelligence decreases. Socioeconomic factors were controlled for with a general abilities index.

Although the exact mechanism for a correlated intelligence with CAG repeats in HTT isn’t well understood, the research paves the road for future studies. The researchers should look for a pathway for a more concrete, scientific explanation for the intelligence correlation.


  1. J. Lee, et al., Effect of trinucleotide repeats in the Huntington’s gene on intelligence. EbioMedicine (2018). doi: 10.1016/j.ebiom.2018.03.031.
  2. Image retrieved from:

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