LRRK2 mutations in Parkinson disease; a sex effect or lack thereof? A meta-analysis

Background: It is currently under debate whether there is a sex effect in LRRK2-associated Parkinson disease (PD), as several studies suggested such effect while others did not. Methods: All case-control studies describing LRRK2 mutations and PD were examined, and papers with data on sex and LRRK2 mutations in both patients and controls were included (n=17) in a sex-stratified meta-analysis. Additional studies (n=33) that included data on male:female ratio only in patients with LRRK2 mutations, were included in further analysis of male:female ratio in LRRK2-assocoiated PD patients. Results: Similar risk estimates were calculated for men and women. Among men, LRRK2 mutation carriers had a pooled OR for PD of 4.20 (95% CI 2.95-5.99, p<0.0001) and among women, LRRK2 mutation carriers had a pooled OR for PD of 4.73 (95% CI 3.26-6.86, p<0.0001). Similar risk estimates for men and women were also observed when analysing specific LRRK2 mutations. A total of 1080 LRRK2-associated PD patients with sex information were identified. The male:female ratio was 1.02:1.00 (50.6% men and 49.4% women). Conclusion: While sporadic PD is characterized by a sex effect, with more affected men than women, LRRK2-associated PD lacks a sex effect, as typically seen in autosomal dominant traits.