J N Foo1,2, L C Tan3, W-L Au3, K-M Prakash3, J Liu2, E-K Tan3,4. 1. Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore. 2. Human Genetics, Genome Institute of Singapore, A*STAR, Singapore. 3. Department of Neurology, National Neuroscience Institute, Singapore. 4. Duke-NUS Graduate Medical School, Singapore, Singapore.
Abstract
BACKGROUND AND PURPOSE: Genetic variability in DNM3 has been shown to modify age of onset of Parkinson's disease (PD) among LRRK2 Gly2019Ser carriers in North African Arab-Berber populations. In Asian populations, the Gly2019Ser mutation is rare or absent but two other LRRK2 variants, Gly2385Arg and Arg1628PPro, increase PD risk. We aimed to determine whether the DNM3 locus was associated with age of PD onset in both carriers and non-carriers of LRRK2 risk variants in Asians. METHODS: We analyzed the association of DNM3 rs2421947 genotypes with age of PD onset in 3645 Chinese samples, of which 369 carried at least one of two Asian LRRK2 risk variants. RESULTS: DNM3 rs2421947 genotypes were not associated with age of PD onset in Chinese samples. We observed no heterogeneity in the effect of rs2421947 between the Asian LRRK2 risk variant carriers and non-carriers. CONCLUSIONS: DNM3 rs2421947 was not associated with age of PD onset in LRRK2 risk variant carriers and non-carriers in Chinese samples. Further studies in other Asian populations will be of interest.
BACKGROUND AND PURPOSE: Genetic variability in DNM3 has been shown to modify age of onset of Parkinson's disease (PD) among LRRK2 Gly2019Ser carriers in North African Arab-Berber populations. In Asian populations, the Gly2019Ser mutation is rare or absent but two other LRRK2 variants, Gly2385Arg and Arg1628PPro, increase PD risk. We aimed to determine whether the DNM3 locus was associated with age of PD onset in both carriers and non-carriers of LRRK2 risk variants in Asians. METHODS: We analyzed the association of DNM3rs2421947 genotypes with age of PD onset in 3645 Chinese samples, of which 369 carried at least one of two Asian LRRK2 risk variants. RESULTS:DNM3rs2421947 genotypes were not associated with age of PD onset in Chinese samples. We observed no heterogeneity in the effect of rs2421947 between the Asian LRRK2 risk variant carriers and non-carriers. CONCLUSIONS:DNM3rs2421947 was not associated with age of PD onset in LRRK2 risk variant carriers and non-carriers in Chinese samples. Further studies in other Asian populations will be of interest.
Authors: Emmeline E Brown; Cornelis Blauwendraat; Joanne Trinh; Mie Rizig; Mike A Nalls; Etienne Leveille; Jennifer A Ruskey; Hallgeir Jonvik; Manuela M X Tan; Sara Bandres-Ciga; Sharon Hassin-Baer; Kathrin Brockmann; Jon Infante; Eduardo Tolosa; Mario Ezquerra; Sawssan Ben Romdhan; Mustapha Benmahdjoub; Mohamed Arezki; Chokri Mhiri; John Hardy; Andrew B Singleton; Roy N Alcalay; Thomas Gasser; Donald G Grosset; Nigel M Williams; Alan Pittman; Ziv Gan-Or; Ruben Fernandez-Santiago; Alexis Brice; Suzanne Lesage; Matthew Farrer; Nicholas Wood; Huw R Morris Journal: Neurobiol Aging Date: 2020-07-13 Impact factor: 4.673