Reactivity of the Serum from A-Bomb Survivors with the Tissues of Stomach, Liver and Kidney of Normal Rats

In order to evaluate delayed effects of radiation on pathological immune response an attempt was made to detect antibodies in the serum of atomic bomb survivors against kidney, liver, and parietal cells from rats. The following results were observed. Analysis of changes in antibody detection frequencies by age and exposure dose without considering sex showed that the rates for those exposed to 100 + rad showed a trend to increase with age for all three organs (P<0.01). However, in the 0 rad group, a significant trend to increase with age was noted for anti-kidney and antiliver antibodies only (P<0.01 for both). Analysis of changes in antibody detection frequencies by sex, age, and exposure dose showed that the detection frequencies increased significantly with age for all three organs in males exposed to 100 + rad (P < 0.05), but only the anti-liver antibody frequency increased significantly with age in males in the O rad exposure group. Females failed to shown any statistical changes in any exposure group

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

Sample size and characteristics of the discovery and replication datasets.

<p>Sample size and characteristics of the discovery and replication datasets.</p

Top-ranked genome-wide association results in the Japanese discovery (Stage 1) sample (P<2.5×10⁻⁵) and their replication in Japanese (Stage 2).

<p>CH:MB, chromosome:position (in megabasepairs, build 19); MA, minor allele; MAF, minor allele frequency; # SNPs, the number of SNPs for which P≤1×10⁻⁴ in the discovery (Stage 1) sample; OR, odds ratio; <i>P</i> P-value;</p><p>Selected SNPs represent the strongest association within each locus.</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