Ziv Gan-Or1, Claire S Leblond2, Victoria Mallett3, Avi Orr-Urtreger4, Patrick A Dion5, Guy A Rouleau6. 1. Montreal Neurological Institute, McGill University, Montréal, QC, Canada; Department of Human Genetics, McGill University, Montréal, QC, Canada. Electronic address: ziv.gan-or@mail.mcgill.ca. 2. Montreal Neurological Institute, McGill University, Montréal, QC, Canada; Department of Human Genetics, McGill University, Montréal, QC, Canada. 3. Montreal Neurological Institute, McGill University, Montréal, QC, Canada. 4. The Genetic Institute, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel. 5. Montreal Neurological Institute, McGill University, Montréal, QC, Canada; Department of Neurology and Neurosurgery, McGill University, Montréal, QC, Canada. 6. Montreal Neurological Institute, McGill University, Montréal, QC, Canada; Department of Neurology and Neurosurgery, McGill University, Montréal, QC, Canada. Electronic address: guy.rouleau@mcgill.ca.
Abstract
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.
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 PDpatients. 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 PDpatients 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.
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Authors: Tanya Simuni; Michael C Brumm; Liz Uribe; Chelsea Caspell-Garcia; Christopher S Coffey; Andrew Siderowf; Roy N Alcalay; John Q Trojanowski; Leslie M Shaw; John Seibyl; Andrew Singleton; Arthur W Toga; Doug Galasko; Tatiana Foroud; Kelly Nudelman; Duygu Tosun-Turgut; Kathleen Poston; Daniel Weintraub; Brit Mollenhauer; Caroline M Tanner; Karl Kieburtz; Lana M Chahine; Alyssa Reimer; Samantha Hutten; Susan Bressman; Kenneth Marek Journal: Mov Disord Date: 2020-02-19 Impact factor: 10.338
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