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Analysis of genetic risk factors in Japanese patients with Parkinson’s disease


Parkinson’s disease (PD) is caused by a combination of genetic and environmental factors. Notably, genetic risk factors vary according to ethnicity and geographical regions, and few studies have analyzed the frequency of PD causative genes in Japanese patients. Therefore, we performed genetic analyses of Japanese patients with PD. We recruited 221 participants, including 26 patients with familial PD. Genetic risk factors were evaluated by target sequencing and gene dosage analysis. We detected the genetic risk factors in 58 cases (26.2%) and classified patients into three groups to clarify the differences in genetic risk factors by age at onset (AAO). The early-onset group (AAO < 50 years) included 18 cases (44.7%), who tended to have a larger number of genetic risk factors than the later-onset groups. Regarding the AAO for each causative gene, patients with PRKN variants were significantly younger at onset than those bearing LRRK2 variants. LRRK2 variants showed similar frequency in each AAO group. Of note, we identified two novel variants. Patients with early-onset PD have more genetic risk factors than patients with late-onset PD. In Japanese patients with PD, PRKN, and LRRK2 were the major PD-related genes. Particularly, LRRK2 was a common genetic factor in all age groups because of the presence of the Asian-specific variant such as LRRK2 p.G2385R. Accumulation of genetic and clinical data can contribute to the development of treatments for PD.

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We are grateful to the patients who participated in this study. We thank Ms. Eiko Nakajima for providing technical assistance.


YI receives support from Grants-in-Aid from the Research Committee of CNS Degenerative Diseases, the Ministry of Health, Labour and Welfare of Japan (20FC1049) and HK receives support from The Takeda Science Foundation.

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The study was designed by YK, HMorino, and HK. Statistical analysis and interpretation were performed by YK, HMorino, and RO. Sample preparation and genotyping were performed by YK and KK. Patient recruitment was performed by TK, MK, TT, YI, HMorino, and HK. Review and critique were performed by HMaruyama and HK. Drafting and revising of the manuscript were performed by all authors. All authors have read and approved the final article.

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Correspondence to Hiroyuki Morino.

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Kanaya, Y., Kume, K., Morino, H. et al. Analysis of genetic risk factors in Japanese patients with Parkinson’s disease. J Hum Genet 66, 957–964 (2021).

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