Parkinson Disease Onset Linked to LRRK2 Variants

HealthDay News — The presence of multiple LRRK2 risk variants is associated with a younger age at onset (AAO) of Parkinson disease (PD), according to a research letter published in JAMA Neurology.

Bin Xiao, MD, PhD, from the National Neuroscience Institute in Singapore, and colleagues assessed 1284 patients with PD for the LRRK2 risk variants S1647T, R1628P, and G2385R. The variants were genotyped by TaqMan real-time polymerase chain reaction; 10% of the results were checked for errors using Sanger sequencing. The AAO of carriers and noncarriers of LRRK2 variants was compared.

The researchers found that the mean AAO was 62.3 years among all patients with PD, with women developing PD later than men (63.3 vs 61.6 years). Overall, 789 participants carried at least one of the S1647T, R1628P, and G2385R risk variants and 495 did not. The mean AAO was 62.5 years among participants with no variants, compared with 62.3 years (95% CI, -1.35-1.18) for participants with 1 risk variant, 61.3 years (95% CI, -0.7- 3.15) for those with 2 risk variants, and 52.6 years (95% CI, 3.29-16.51) for those with all 3 risk variants. After adjustment for multiple testing, the difference between carriers with all 3 variants and noncarriers remained significant.

Related Articles

“These coding variants may contribute to PD development through distinct mechanisms and additively lower the AAO of PD,” the authors wrote. “Our data suggest that increases in the genetic burden of LRRK2 variants may be associated with an earlier AAO in PD.”


Xiao B, Deng X, Ng EY, et al. Association wof LRRK2 haplotype with age at onset in Parkinson’s disease [published online November 13, 2017]. JAMA Neurol. doi:10.1001/jamaneurol.2017.3363