Related Experiment Video
Updated: Jan 6, 2026
Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
Midnolin is a confirmed genetic risk factor for Parkinson's disease
Yutaro Obara1, Hidenori Sato2, Takahiro Nakayama3
1Department of Pharmacology, Yamagata University School of Medicine, Yamagata, Japan.
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.
Insights
Midnolin (MIDN) gene copy number loss is strongly associated with Parkinson's disease (PD) risk in both British and Japanese populations. This finding confirms MIDN as a significant genetic risk factor for PD development.
Area of Science:
- Genetics
- Neuroscience
- Molecular Biology
Background:
- Parkinson's disease (PD) pathogenesis remains largely unknown for sporadic cases, despite identified genes in familial forms.
- Previous research linked Midnolin (MIDN) to PD in a Japanese cohort, showing its role in neurite outgrowth and Parkin regulation.
Purpose of the Study:
- To replicate the genetic association between the MIDN gene and Parkinson's disease in a large British population.
- To investigate the role of MIDN copy number variations and single-nucleotide polymorphisms in PD etiology.
Main Methods:
- A case-control genome-wide association study was conducted on a British cohort.
- Analysis included 2,168 PD patients and 2,860 controls, examining MIDN gene copy number variations and single-nucleotide polymorphisms.
Main Results:
- Significant copy number loss of the MIDN gene was observed in PD patients (OR = 4.35, P < 2.2 × 10⁻¹⁶).
- A large deletion (>50,000 bp) in MIDN dramatically increased PD risk (OR = 22.3, P = 3.59 × 10⁻¹⁵).
- No significant association was found for common single-nucleotide polymorphisms (rs3746106, rs3746107).
Conclusions:
- The study confirms a strong genetic association of MIDN with Parkinson's disease in a British population.
- These findings, combined with previous Japanese cohort data, establish MIDN as a confirmed and universal genetic risk factor for PD.
Related Concept Videos
01:37Neural Regulation
01:24Parkinson's Disease: Treatment
Parkinson's Disease is primarily a result of the loss of dopaminergic neurons in the substantia nigra pars compacta. The cornerstone of...
01:15Parkinson's Disease: Overview
01:28Human Genetics
The complex relationship between genetics and psychology is observable through common biological components such...
01:05Single Nucleotide Polymorphisms-SNPs