講演情報
[P12-12]日本人および民族間横断的ゲノムワイド関連解析によるレビー小体認知症感受性座位の探索
○光森 理紗1, 浅海 裕也1, 重水 大智1,2, 秋山 真太郎1, 森園 隆1, 新飯田 俊平3, 尾崎 浩一1,2 (1.国立長寿医療研究センター 研究所 メディカルゲノムセンター, 2.理化学研究所 生命医科学研究センター, 3.国立長寿医療研究センター 研究所 研究推進基盤センター)
Dementias are common multifactorial neurodegenerative disorder with complex interactions between genetic and environmental risk factors. Lewy body dementia (DLB) is the second most common disorder following Alzheimer disease (AD). DLB is caused by a-synuclein proteins in the form of Lewy bodies that are deposited in cortical and limbic. Recent large scale whole-genome sequencing analysis with Caucasian descent has identified five genetic susceptibility loci for DLB, whereas reports of large scale genetic analysis with Asian are relatively modest. To clarify genetic architecture in the pathogenesis of DLB in Japanese, we have conducted genome wide association study (GWAS) using ethnicity specific genotyping array, Asia screening array, with 221 DLB and 6,113 controls recruited at the National Center for Geriatrics and Gerontology biobank. We identified six genetic susceptibility loci at suggestive significance (P≦1.0×10-6), including APOE , known locus associated with the increased risk of DLB and AD in Caucasians. Subsequent meta-analysis combining the results from the Japanese and the European GWAS in the UK biobank also identified a novel candidate locus on chromosome 10 for DLB susceptibility at suggestive significance. We are now focusing on expression quantitative trait loci (eQTL), and further conducting the gene-based association analysis, network analysis and construction of polygenic risk scores, which could contribute to understanding the polygenic mechanisms for DLB.