Huntington disease reduced penetrance alleles occur at high frequency in the general population

Chris Kay, Jennifer A. Collins, Zosia Miedzybrodzka, Steven J. Madore, Erynn S. Gordon, Norman Gerry, Mark Davidson, Ramy A. Slama, Michael R Hayden

Research output: Contribution to journalArticlepeer-review

60 Citations (Scopus)


Objective: To directly estimate the frequency and penetrance of CAG repeat alleles associated with Huntington disease (HD) in the general population.

Methods: CAG repeat length was evaluated in 7,315 individuals from 3 population-based cohorts from British Columbia, the United States, and Scotland. The frequency of ≥36 CAG alleles was assessed out of a total of 14,630 alleles. The general population frequency of reduced penetrance alleles (36–39 CAG) was compared to the prevalence of patients with HD with genetically confirmed 36–39 CAG from a multisource clinical ascertainment in British Columbia, Canada. The penetrance of 36–38 CAG repeat alleles for HD was estimated for individuals ≥65 years of age and compared against previously reported clinical penetrance estimates.

Results: A total of 18 of 7,315 individuals had ≥36 CAG, revealing that approximately 1 in 400 individuals from the general population have an expanded CAG repeat associated with HD (0.246%). Individuals with CAG 36–37 genotypes are the most common (36, 0.096%; 37, 0.082%; 38, 0.027%; 39, 0.000%; ≥40, 0.041%). General population CAG 36–38 penetrance rates are lower than penetrance rates extrapolated from clinical cohorts.
Original languageEnglish
Pages (from-to)282-288
Number of pages7
Issue number3
Early online date22 Jun 2016
Publication statusPublished - Jul 2016


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