Replication study for R wave in V5.

<p>Replication study for R wave in V5.</p

Additional file 1: Figure S1. of Validation of genotype imputation in Southeast Asian populations and the effect of single nucleotide polymorphism annotation on imputation outcome

Long distance LD pr. Mb separated by the chromosome for each population LD for each SNP pair with a distance between 10 kb and 1 Mb taken into account. Figure S2. Accuracy and yield of imputation between each location of SNPs. Figure S3. Comparing minor allele frequencies of SNPs between imputed and actual genotypes before quality control of imputed results separately plot by each SNP location. Figure S4. Comparing allele frequencies of SNPs between imputed and actual genotypes after quality control of imputed results separately plotted by each SNP location. Figure S5. Proportion of SNPs with lower AF after imputation vs initial AF. Figure S6. Comparing p-values between cases and controls of SNPs between imputed and actual genotypes before quality control of imputed results separately plotted by each SNP location. Figure S7. Comparing p-values between cases and controls of SNPs between imputed and actual genotypes after quality control of imputed results separately plotted according to each SNP location. Figure S8. Average linkage disequilibrium as r-squared for each region. SNPs were assigned to gene locations. Figure S9. LD, measured as r2, plotted against physical distance. (PDF 1286 kb

The results of GWAS on corrected electrocardiographic RV5 voltages.

<p>The Manhattan plots and quantile-quantile plots of genome-wide association results for RV5 from analysis of JPDSC datasets are shown.</p

Results of GWAS for R wave in V5.

<p>Results of GWAS for R wave in V5.</p

Pairwise Kinship Analysis by the Index of Chromosome Sharing Using High-Density Single Nucleotide Polymorphisms

<div><p>We developed a new approach for pairwise kinship analysis in forensic genetics based on chromosomal sharing between two individuals. Here, we defined “index of chromosome sharing” (<i>ICS</i>) calculated using 174,254 single nucleotide polymorphism (SNP) loci typed by SNP microarray and genetic length of the shared segments from the genotypes of two individuals. To investigate the expected <i>ICS</i> distributions from first- to fifth-degree relatives and unrelated pairs, we used computationally generated genotypes to consider the effect of linkage disequilibrium and recombination. The distributions were used for probabilistic evaluation of the pairwise kinship analysis, such as likelihood ratio (LR) or posterior probability, without allele frequencies and haplotype frequencies. Using our method, all actual sample pairs from volunteers showed significantly high LR values (i.e., ≥ 10⁸); therefore, we can distinguish distant relationships (up to the fifth-degree) from unrelated pairs based on LR. Moreover, we can determine accurate degrees of kinship in up to third-degree relationships with a probability of > 80% using the criterion of posterior probability ≥ 0.90, even if the kinship of the pair is totally unpredictable. This approach greatly improves pairwise kinship analysis of distant relationships, specifically in cases involving identification of disaster victims or missing persons.</p></div

Large-Scale East-Asian eQTL Mapping Reveals Novel Candidate Genes for LD Mapping and the Genomic Landscape of Transcriptional Effects of Sequence Variants

<div><p>Profiles of sequence variants that influence gene transcription are very important for understanding mechanisms that affect phenotypic variation and disease susceptibility. Using genotypes at 1.4 million SNPs and a comprehensive transcriptional profile of 15,454 coding genes and 6,113 lincRNA genes obtained from peripheral blood cells of 298 Japanese individuals, we mapped expression quantitative trait loci (eQTLs). We identified 3,804 <i>cis-</i>eQTLs (within 500 kb from target genes) and 165 <i>trans</i>-eQTLs (>500 kb away or on different chromosomes). <i>Cis-</i>eQTLs were often located in transcribed or adjacent regions of genes; among these regions, 5′ untranslated regions and 5′ flanking regions had the largest effects. Epigenetic evidence for regulatory potential accumulated in public databases explained the magnitude of the effects of our eQTLs. <i>Cis</i>-eQTLs were often located near the respective target genes, if not within genes. Large effect sizes were observed with eQTLs near target genes, and effect sizes were obviously attenuated as the eQTL distance from the gene increased. Using a very stringent significance threshold, we identified 165 large-effect <i>trans</i>-eQTLs. We used our eQTL map to assess 8,069 disease-associated SNPs identified in 1,436 genome-wide association studies (GWAS). We identified genes that might be truly causative, but GWAS might have failed to identify for 148 out of the GWAS-identified SNPs; for example, <i>TUFM</i> (<i>P</i> = 3.3E-48) was identified for inflammatory bowel disease (early onset); <i>ZFP90</i> (<i>P</i> = 4.4E-34) for ulcerative colitis; and <i>IDUA</i> (<i>P</i> = 2.2E-11) for Parkinson's disease. We identified four genes (<i>P</i><2.0E-14) that might be related to three diseases and two hematological traits; each expression is regulated by <i>trans</i>-eQTLs on a different chromosome than the gene.</p></div

Additional file 2: Table S1. of Validation of genotype imputation in Southeast Asian populations and the effect of single nucleotide polymorphism annotation on imputation outcome

Summary of SNPs used in study of SNP annotation to imputation outcome. (XLS 26 kb

Trivalent inactivated influenza vaccine response and immunogenicity assessment after one week and three months in repeatedly vaccinated adults

The influenza vaccine administrated every year is a recommended infection control procedure for individuals above the age of six months. However, the effectiveness of repeated annual vaccination is still an active research topic. Therefore, we investigated the vaccine immunogenicity in two independent groups: previously vaccinated versus non-vaccinated individuals at three time points; prior vaccination, one week and three months post vaccination. The assessment enabled us to evaluate the elicited immune responses and the durability of the induced protection in both groups. A research study was conducted to assess the immunogenicity of a single dose of Trivalent Inactivated Influenza Vaccine (A/H1N1, A/H3N2, and B) in 278 healthy adults aged between 32 and 66 years. Almost half of the participants, 140 (50·36%), received influenza vaccination at least once precursor to past influenza seasons. One blood sample was taken prior to vaccination for complete blood analysis and baseline immunogenicity assessment. The selected study participants received a single vaccine dose on the first day, and then followed up for three months. Two blood samples were taken after one week and three months post vaccination, respectively, for vaccine immunogenicity assessment. Before vaccination, the seroprotection, defined as a hemagglutination-inhibiting titer of =>1:40, was detected for the three vaccine virus strains in 20 previously vaccinated participants (14·29%) [8·95%, 21·2%]. We compared the overall vaccine response for the three virus strains using a normalized response score calculated from linearly transformed titer measurements; the score before vaccination was 84% higher in the previously vaccinated group and the mean difference between the two groups was statistically significant. Three months post-vaccination, we didn’t find a significant difference in vaccine responses; the number of fully seroprotected individuals became 48 (34·29%) [26·48%, 42·77%] in the previously vaccinated group and 59 (42·75%) [34·37%, 51·45%] in the non-vaccinated group. The calculated response score was almost equal in both groups and the mean difference was no longer statistically significant. Our findings suggest that a single dose of influenza vaccine is equally protective after three months for annually vaccinated adults and first-time vaccine receivers.</p

Cis-eQTL map.

<p>–log₁₀ P values of cis-eQTLs are plotted against the respective chromosomal positions. eQTLs for mRNA transcripts are shown in red; lincRNA transcripts are shown in green; and other transcripts are shown in black. The vertical dashed lines separate chromosomes.</p

The range of <i>ICS</i> values in each Hummel’s predicate for kinship determination.

<p><i>ICS</i> values for (A) collateral relatives and (B) lineal relatives. Solid lines indicate the estimated log-normal distributions of the <i>ICS</i>_<i>C</i> and <i>ICS</i>_<i>L</i> values. The colors in the bar under the distributions indicate the range of the <i>ICS</i>_<i>C</i> and <i>ICS</i>_<i>L</i> values that can be obtained from the posterior probabilities corresponding to each Hummel’s predicate for each relationship. The plots indicate the <i>ICS</i>_<i>C</i> and <i>ICS</i>_<i>L</i> values calculated by the rest of the actual sample pairs. All actual L-1 pairs were almost equal to the maximum value of <i>ICS</i>_<i>L</i> (i.e., 3662.522) and are indicated in red. * The distribution of UN is partially displayed because the density of the estimated distribution of UN is high.</p