Objective: To 1) determine the distribution of CAG repeats of the Huntingtin gene in a Swedish general population sample, 2) explore the phenotype caused by specific CAG repeat numbers, with focus on the Intermediate Alleles (IA, 27-35 repeats).

Background: Behavioral symptoms have been attributed to carrying IAs. However, these findings come from Huntington’s disease families and confounding by genetic modifiers cannot be ruled out.

Method: DNA-samples from 8272 individuals were retrieved from a study of first-ever myocardial infarction (MI), thus without connection to HD. Each MI case was (age- and sex-) matched with two controls from the medical biobank of Umeå University Hospital. Baseline self-assessed health and demographic data was collected from participants of the MI-study cohort.

Results: CAG-repeat numbers of 7387 individuals were successfully measured of which 503 subjects (6.8%) were IA-carriers, 30 subjects (0.4%) had a reduced penetrance allele (36-39 repeats), and 2 individuals had a full penetrance allele (>39 repeats). In brief, self-assessed health ratings between carriers of IAs vs. normal alleles did not differ. The analysis was limited by incomplete data on some of the questionnaires.

Conclusion: This population has among the highest ever reported prevalences of IAs and numerically includes the largest single cohort of IAs to date The frequency of reduced penetrance alleles was surprisingly high, 1/250 individuals. While self-assessed health does not seem to depend on carrying IAs, a future national registry-based study of this cohort aims to clarify if IA carriers have excess psychiatric comorbidity.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/intermediate-cag-repeat-length-in-the-htt-gene-and-comorbidity-the-shape-study-swedish-huntingtin-alleles-and-phenotype/