Fig. 5.

Changes of mtDNA variant fractions and pathogenicity in blood during HD progression. (A) Box plots of the variant allele fraction (VAF) changes of preexisting mtDNA heteroplasmies in blood samples of HD patients with and without a progression of disease stage during the follow-up. The P values from t test and Cohen’s d are shown for the difference between stable-stage patients and progressed-stage patients, which were computed using (from Left to Right in A) all heteroplasmies, heteroplasmies with medium or high pathogenicity, or heteroplasmies with only high pathogenicity. Each red dot in A indicates one heteroplasmy with its VAF change during the follow-up indicated by the value on the y axis. (B and C) The correlations between the VAF changes of preexisting nonsynonymous heteroplasmies and their CADD pathogenicity scores among (B) stable-stage patients and among (C) progressed-stage patients. The CADD scores are shown with the inverse normal transformed values, which increase with the chance of a heteroplasmy being pathogenic. The dashed lines represent the fitted regression lines.