13 research outputs found
細胞外ラミニンはインテグリンβ1-ILK-βカテニン-JUN経路を介して多能性幹細胞の造血能を制御する
京都大学新制・課程博士博士(医学)甲第23383号医博第4752号新制||医||1052(附属図書館)京都大学大学院医学研究科医学専攻(主査)教授 河本 宏, 教授 髙折 晃史, 教授 金子 新学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA
SORL1 Is Genetically Associated with Late-Onset Alzheimer’s Disease in Japanese, Koreans and Caucasians
To discover susceptibility genes of late-onset Alzheimer’s disease (LOAD), we conducted a 3-stage genome-wide association study (GWAS) using three populations: Japanese from the Japanese Genetic Consortium for Alzheimer Disease (JGSCAD), Koreans, and Caucasians from the Alzheimer Disease Genetic Consortium (ADGC). In Stage 1, we evaluated data for 5,877,918 genotyped and imputed SNPs in Japanese cases (n = 1,008) and controls (n = 1,016). Genome-wide significance was observed with 12 SNPs in the APOE region. Seven SNPs from other distinct regions with p-values ,261025 were genotyped in a second Japanese sample (885 cases, 985 controls), and evidence of association was confirmed for one SORL1 SNP (rs3781834, P=7.3361027 in the combined sample). Subsequent analysis combining results for several SORL1 SNPs in the Japanese, Korean (339 cases, 1,129 controls) and Caucasians (11,840 AD cases, 10,931 controls) revealed genome wide significance with rs11218343 (P=1.7761029) and rs3781834 (P=1.0461028). SNPs in previously established AD loci in Caucasians showed strong evidence of association in Japanese including rs3851179 near PICALM (P=1.7161025) and rs744373 near BIN1 (P = 1.3961024). The associated allele for each of these SNPs was the same as in Caucasians. These data demonstrate for the first time genome-wide significance of LOAD with SORL1 and confirm the role of other known loci for LOAD in Japanese. Our study highlights the importance of examining associations in multiple ethnic populations
Tyrosyl-tRNA synthetase stimulates thrombopoietin-independent hematopoiesis accelerating recovery from thrombocytopenia
Correction: Is Genetically Associated with Late-Onset Alzheimer’s Disease in Japanese, Koreans and Caucasians.
Correction: SORL1 Is Genetically Associated with Late-Onset Alzheimer’s Disease in Japanese, Koreans and Caucasians
Regional association plot for the <i>SORL1</i> region on chromosome 11 in the three-stage design.
<p>For each SNP, the chromosomal location is shown on the x-axis and the significance level for association with LOAD is indicated by a –log<sub>10</sub>P value on the y-axis. P-values are expressed as –log<sub>10</sub>(P) (y-axis) for every tested SNP ordered by chromosomal location (x-axis). Genomic position was determined using the NCBI database (Build 37.1). Computed estimates of linkage disequilibrium (LD; r<sup>2</sup>) between SNPs in this region with the top-ranked SNP (rs3781834) in the Japanese discovery (J1) dataset are shown as red circles for r<sup>2</sup>≥0.8, orange circles for 0.5≤r<sup>2</sup><0.8, light blue circles for 0.2≤r<sup>2</sup><0.5, and dark blue circles for r<sup>2</sup><0.2 using hg19/1000 Genomes of Asian populations (ASN; release on November 2010) combined from Han Chinese (CHB) and Japanese (JPT). Meta-analysis <i>P</i>-values are shown as purple diamonds for the Japanese datasets (J1+J2) and all datasets (J1+J2+K+C) including Japanese, Korean (K), and Caucasians (C). Two genome-wide significant SNPs in the final stage (rs3781834 and rs11218343) are presented. The gene structure and reading frame are shown below the plot. Exons are denoted with vertical bars. The LD between rs3781834 and rs11218343 is 0.57 in the ASN reference population.</p
Forest plots of the two most strongly associated SNPs, rs3781834 (A) and rs11218343 (B), in the <i>SORL1</i> region showing the strength and pattern of significance in the Japanese discovery and each replication dataset in the model of adjusting for population structure, age, and sex.
<p>Forest plots of the two most strongly associated SNPs, rs3781834 (A) and rs11218343 (B), in the <i>SORL1</i> region showing the strength and pattern of significance in the Japanese discovery and each replication dataset in the model of adjusting for population structure, age, and sex.</p