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Structural Variants of Midnolin, a Genetic Risk Factor for Parkinson's Disease, in a Yamagata Cohort
Hidenori Sato1, Kuniaki Ishii2, Yutaro Obara2
1Genome Informatics Unit, Institution for Promotion of Medical Science Research, Yamagata University School of Medicine.
Abstract:
Parkinson's disease (PD) is a common neurodegenerative disease. We previously identified Midnolin (MIDN) to be a genetic risk factor for PD in both Yamagata (Japan) and British populations. However, the scale of our previous study was not sufficient to identify MIDN structural variants in the ascertained control of Yamagata Prefecture. We, therefore, reanalyzed MIDN variants in 3021 individuals from Yamagata Prefecture to compare with that in our previous British cohort study. MIDN copy number loss was only found in two cases (0.0662%), which was a lower frequency than that (1.64%) of the previously studied British cohort. Between the Yamagata and British groups, there was significant difference for rs3746106, located in the 5'-UTR of MIDN mRNA (p = 0.0003344, odds ratio 1.143), and for rs3746107, which corresponds to Ala34 (p < 2.2 × 10-16, odds ratio 5.89401). This study indicates that MIDN loss is relatively rare in the general Japanese population. Considering our previous studies that the frequency of MIDN loss is high among patients with PD (10.5 and 6.55% in Yamagata and Britain, respectively), the MIDN variants are much higher genetic risk factors for PD in a Japanese population than in a British population.
Insights
Midnolin (MIDN) loss is rare in the Japanese population but a significant genetic risk factor for Parkinson's disease (PD). This study found MIDN variants pose a higher PD risk in Japanese individuals compared to British cohorts.
Area of Science:
- Genetics
- Neurodegenerative Diseases
- Population Studies
Background:
- Parkinson's disease (PD) is a prevalent neurodegenerative disorder.
- Midnolin (MIDN) has been identified as a genetic risk factor for PD in both Japanese and British populations.
- Previous studies lacked the scale to fully assess MIDN structural variants in Japanese control populations.
Purpose of the Study:
- To re-evaluate MIDN variants in a larger Japanese cohort from Yamagata Prefecture.
- To compare the frequency and significance of MIDN variants between Japanese and British populations concerning PD risk.
Main Methods:
- Analysis of MIDN variants in 3021 individuals from Yamagata Prefecture.
- Comparison of MIDN copy number loss and specific single nucleotide polymorphisms (SNPs) frequencies with a previously studied British cohort.
- Statistical analysis including p-values and odds ratios for identified genetic differences.
Main Results:
- MIDN copy number loss was found at a low frequency (0.0662%) in the Japanese cohort, significantly lower than the British cohort (1.64%).
- Significant differences were observed between Yamagata and British groups for rs3746106 (p=0.0003344, OR=1.143) and rs3746107 (p<2.2×10⁻¹⁶, OR=5.89401).
- MIDN loss is rare in the general Japanese population but frequent in Japanese PD patients (10.5%).
Conclusions:
- MIDN copy number loss is uncommon in the general Japanese population.
- MIDN variants represent a substantially higher genetic risk factor for Parkinson's disease in the Japanese population compared to the British population.
- Further research into MIDN's role in PD pathogenesis across diverse ethnic groups is warranted.
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