Resequencing analysis of the 19q25.3 locus associated with Moyamoya disease in Japan

2015 Fiscal Year Final Research Report

• Project/Area Number: 26670649
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neurosurgery
• Research Institution: Tokyo Women's Medical University
• Principal Investigator: Akagawa Hiroyuki 東京女子医科大学, 医学部, テニュアトラック准教授 (60398807)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: もやもや病 / 感受性遺伝子 / 連鎖不平衡 / ハプロタイプ

Outline of Final Research Achievements

A founder variant of RNF213 (p.R4810K) was recently identified as a major genetic risk factor for Moyamoya disease (MMD) in Japan. Although the association of p.R4810K was reported to be highly significant and reproducible, the disease susceptibility of other RNF213 variants remain largely unknown. In this study, we performed resequencing analysis of this locus and evaluated the detected variants for their associations with MMD. A total of 30 rare missense variants with minor allele frequencies <1% were identified among 370 combined patients and 279 combined controls in Japan. The variable threshold test using Combined Annotation-Dependent Depletion revealed that the frequency of potentially functional variants was significantly higher in patients than in controls (permutation Pmin=0.045). Our analysis also revealed that approximately 20% of Japanese MMD patients did not harbor susceptibility variants of RNF213, indicating the presence of other susceptibility genes to MMD.

Free Research Field

脳神経外科学