Association of <i>LRRK2</i> Haplotype With Age at Onset in Parkinson Disease

Abstract

Genetic factors provide valuable clues to the pathogenesis of Parkinson disease (PD), owing to their roles in disease development. Mutations in 9 genes have been conclusively linked to monogenic PD over the past 2 decades. 1 Among Asian populations, the S1647T, R1628P, and G2385R variants of LRRK2 are established risk factors for PD. 2 Clinically, patients who have these LRRK2 risk variants share substantial similarities with patients with sporadic PD. It has been suggested that the G2385R variant is associated with a lower age at onset (AAO) of PD. 3 However, it is unknown whether the presence of multiple LRRK2 risk variants modulates the AAO of PD. We hypothesize that increases in the genetic burden of LRRK2 risk variants may be associated with a younger AAO. To test this hypothesis, we conducted a correlation study among a cohort of participants with PD who carried the LRRK2 risk variants S1647T, R1628P, and G2385R.