Figure 4.

Pattern of association between Huntington’s disease (HD) symptoms and polygenic risk score (PRS) from psychiatric, neurodegenerative, and cognitive disorders. (A) PRS grouped into psychiatric (black), neurodevelopmental (blue), neurodegenerative (orange), and cognitive (cyan) disorders. Significant correlations between the PRSs associated with HD symptoms are shown by blue (positive correlations) and orange (negative correlations) lines, with line width proportional to the correlation magnitude. Solid lines between PRS and symptoms show associations significant after correcting for 63 PRS-symptom combinations (9 PRS × 7 symptoms) and 6 PRS cutoffs (p < 1.32 × 10⁻⁴). Dashed lines show associations significant after correcting for 63 PRS-symptom combinations (p < 7.94 × 10⁻⁴). Dotted lines show nominally significant associations (p < .05) in PRS-symptom combinations that were part of the primary analysis. Bold lines show PRS-symptom associations that are significant after correcting for other PRS and symptoms (Table 3). (B) Heat map showing correlations between symptoms (numerical values in Supplemental Table S2). All correlations are positive, and statistically significant (p < 2.2 × 10⁻¹⁶). AD, Alzheimer’s disease; ADHD, attention-deficit/hyperactivity disorder; APT, apathy; ASD, autism spectrum disorder; BPD, bipolar disorder; COG, cognitive impairment; DEP, depression; INT, intelligence; IRB, irritability; MDD, major depressive disorder; OCD, obsessive-compulsive disorder; PD, Parkinson’s disease; POB, perseverative/obsessive behavior; PSY, psychosis; SZ, schizophrenia; VAB, violent/aggressive behavior.