Precision medicine of Parkinson disease from the perspective of clinical genetics

Abstract

Genetic insights are increasingly central to precision medicine in Parkinson disease (PD). This article reviews the evolution of clinical genetics in PD and its implications for treatment strategies. We discuss the transition from identifying monogenic causes to understanding complex genetic risks, highlighting recent advances in long–read sequencing that uncover structural variants like PRKN inversions previously missed by standard methods. Furthermore, we discuss the impact of specific genotypes on outcomes of deep brain stimulation, emphasizing the need for genotype–based patient stratification. Finally, we explore the role of genetics in drug development, referencing ongoing trials for LRRK2 and GBA carriers, and the potential of polygenic risk scores to stratify sporadic PD patients. The integration of multi–omics and ancestry–specific genetic data, particularly from Asian populations, is crucial for realizing precision medicine in PD.