Genetic Influences on Restless Legs Syndrome Associated with Early Parkinson’s Disease: A Four-Year Longitudinal Quantitative Imaging Study

Motivation: Restless legs syndrome (RLS) is a sensorimotor disorder that can occur in association with Parkinson's disease (PD). Our understanding of genetic determinants of MRI-derived nigral iron leading to RLS and PD is limited. Goal(s): We investigated genetic underpinnings of brain iron imbalance to elucidate the underlying neurodegeneration mechanisms. Approach: We used quantitative susceptibility mapping and R2* in 3T MRI to obtain regional nigral iron. We obtained polygenic risk scores associated with RLS and iron metabolism disorders. Results: PD patients without RLS exhibited increased longitudinal nigral iron levels. Our observations indicated an association between genetic predisposition and elevated nigral iron levels. Impact: This study demonstrated that PD patients without RLS symptoms exhibit increased longitudinal nigral iron levels, which are correlated with the neuromelanin depigmentation. Our observations indicated an association between genetic predisposition and elevated MRI-derived nigral iron levels.