Fig. 3.

Associations of pathogenic mtDNA variant dosages with HD clinical phenotypes and genetic burden. The pathogenic mtDNA variant dosages were computed using either heteroplasmies with medium or high pathogenicity or heteroplasmies with only high pathogenicity. The significance levels of the associations of pathogenic mtDNA variant dosages with HD clinical phenotypes are shown in A for UHDRS TFC score, in B for total motor score, and in C for symbol digit modalities test score, all of which were assessed with adjustment for age, sex, and CAG repeat length. The significance levels of the associations with HD genetic burden are shown in D for normalized CAG-age product, which were assessed without adding CAG repeat length and age as covariates. The mean ± SEM of the phenotypes in the lymphoblasts with low (<0.05), medium-to-high (0.05–0.3), and high pathogenic mtDNA variant dosages (≥0.3) are illustrated in each panel.