No evidence for DNM3 as genetic modifier of age at onset in idiopathic Parkinson's disease

Parkinson's disease (PD) is a disorder with highly variable clinical phenotype. The identification of genetic variants modifying age at onset and other traits is of great interest because it may provide insight into disease mechanisms and potential therapeutic targets. A variant in the DNM3 gene (rs2421947) has been reported as a genetic modifier of age at onset in LRRK2-associated PD. To test the possible effect of genetic variation in DNM3 on age at onset in idiopathic PD, we examined rs2421947 in a total of 5918 patients with PD from seven data sets. We also assessed the potential effect of all common variants in the DNM3 locus. There was no significant association between rs2421947 and age at onset in any of the individual studies. Meta-analysis of the seven studies was nonsignificant and the between-study heterogeneity was minimal. No other common variants within the DNM3 locus affected age at onset. In conclusion, we find no evidence of an association between DNM3 variants and age at onset in idiopathic PD.