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- Title
Midnolin is a confirmed genetic risk factor for Parkinson's disease.
- Authors
Obara, Yutaro; Sato, Hidenori; Nakayama, Takahiro; Kato, Takeo; Ishii, Kuniaki
- Abstract
Objective: Genetic analysis of patients with familial Parkinson's disease (PD) identified many causative genes. However, the majority of PD cases are sporadic, and the mechanisms of onset still remain unclear. Previously, we found that Midnolin (MIDN) is associated with PD in a Yamagata (Japan) cohort study and that MIDN regulates neurite outgrowth and Parkin expression in neuronal cells. In the present study, we aimed to replicate the genetic association between MIDN and PD in a large British population cohort. Methods: In this replication study, we analyzed the copy number variations and single‐nucleotide polymorphisms of the MIDN gene in a large British population on a case–control genome‐wide association study dataset including 2,860 controls and 2,168 PD patients. Results: There was significant copy number loss in the MIDN gene with an odds ratio of 4.35 (P < 2.2 × 10−16). Furthermore, there were many patients in both the British and Yamagata case groups who have a long spanning deletion. The odds ratio dramatically increased to 22.3 (P = 3.59 × 10−15) when a deletion spanning more than 50,000 bp was defined as the copy number loss. There were no significant differences between the controls and study cases for two relatively frequent single‐nucleotide polymorphisms (rs3746106 and rs3746107). Interpretation: We showed the strong genetic association of MIDN with PD development in a British population and in a Japanese population, suggesting MIDN is a confirmed and universal genetic risk factor for PD.
- Subjects
PARKINSON'S disease; DISEASE risk factors; ODDS ratio
- Publication
Annals of Clinical & Translational Neurology, 2019, Vol 6, Issue 11, p2205
- ISSN
2328-9503
- Publication type
Article
- DOI
10.1002/acn3.50914