*2.1. Participants*

For these analyses, we utilized data from the Kids-HD and Kids-JOHD studies [11–14]. Both studies were longitudinal neuroimaging studies that ran in parallel. They recruited participants from around the country who were between the ages of 6 and 26 years old to the University of Iowa. The Kids-HD study recruited participants with a family history of HD (parent or grandparent with a known history of HD). These participants underwent genetic testing to determine whether they were gene carriers of the mutation that causes HD. The results of this genetic testing were not revealed to the participants, their family members, or the research sta ff. One research team member received the genetic results and anonymized them. This allowed for the ethical conduct of genetic testing in children. Additionally, the Kids-HD study recruited a cohort of healthy controls without a family history of HD. For the present analysis, all participants from the Kids-HD study with a CAG repeat length of less than 36 were included in the GNE group. The Kids-JOHD study, in comparison, recruited participants with a known diagnosis of JOHD based on molecular confirmation and a diagnosis provided by a neurologist. Participants with a CAG repeat length of 36 or above who were not symptomatic were excluded from the current analysis.

The JOHD group was first evaluated as a whole. We then split the group into those with childhood-onset JOHD and those with adolescent-onset JOHD. Childhood-onset JOHD is defined as an age of motor diagnosis that occurred before the age of 13, while adolescent-onset JOHD occurred between the ages of 13 and 21.

There were 27 participants in the JOHD group accounting for 64 visits, and there were 259 participants in the GNE group accounting for 395 visits. Among the JOHD group, three participants had five visits, two participants had four visits, five participants had three visits, nine participants had two visits, and eight participants only had one visit. In the GNE group, 12 participants had four visits, 21 participants had three visits, 58 participants had two visits, and 168 participants only had one visit. Among the JOHD group, 11 of the 27 participants were classified as having adolescent-onset JOHD and the other 16 were classified as having childhood-onset JOHD.

#### *2.2. Statistical Analyses*

For the primary outcome of interest, the physiologic measures of resting heart rate (rHR), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were analyzed. These measures were collected in the Clinical Research Unit at the University of Iowa by trained professionals with equipment that is well maintained and calibrated regularly. We constructed linear mixed-e ffects regression models to compare the estimated mean di fferences in these measures between the GNE group and the JOHD group controlling for age, sex, the use of medications that may increase blood pressure, the use of medications that may decrease blood pressure and parental socioeconomic status as well as random effects per participant and per family to account for similarities among siblings. Because we were investigating children and young adults, the use of medications, such as stimulants, that may impact blood pressure were controlled for. Medications that were considered to increase blood pressure were stimulants, including amphetamine and methylphenidate-based products. Medications that were considered to lower blood pressure were carbidopa-levodopa, clonidine, guanfacine, and any anti-hypertensive medications. These models were run to first evaluate the JOHD group together, and then again to compare the childhood-onset JOHD and adolescent-onset JOHD groups to the GNE groups. We performed two unplanned sensitivity analyses. First, we repeated the primary analyses that compared rHR, SBP, and DBP between the JOHD participants and the control group after removing all participants visits from participants who were using medications that increased or decreased blood pressure. Next, we evaluated the relationship between duration of disease and rHR, SBP, and DBP among participants in the JOHD group only using linear mixed-effects regression analyses. Since these models only included participants with JOHD, we added CAG repeat length as a covariate in the models. The models were also adjusted for age, the use of medications that increase blood pressure, and the use of medications known to decrease blood pressure.

RStudio was used for all statistical analyses and a *p*-value of <0.05 was considered statistically significant.
