Transition Matrix Monte Carlo Reweighting and Dynamics

We study an induced dynamics in the space of energy of single-spin-flip Monte Carlo algorithm. The method gives an efficient reweighting technique. This dynamics is shown to have relaxation times proportional to the specific heat. Thus, it is plausible for a logarithmic factor in the correlation time of the standard 2D Ising local dynamics.Comment: RevTeX, 5 pages, 3 figure

Are C-Reactive Protein Associated Genetic Variants Associated with Serum Levels and Retinal Markers of Microvascular Pathology in Asian Populations from Singapore?

Introduction:C-reactive protein (CRP) levels are associated with cardiovascular disease and systemic inflammation. We assessed whether CRP-associated loci were associated with serum CRP and retinal markers of microvascular disease, in Asian populations.Methods:Genome-wide association analysis (GWAS) for serum CRP was performed in East-Asian Chinese (N = 2,434) and Malays (N = 2,542) and South-Asian Indians (N = 2,538) from Singapore. Leveraging on GWAS data, we assessed, in silico, association levels among the Singaporean datasets for 22 recently identified CRP-associated loci. At loci where directional inconsistencies were observed, quantification of inter-ethnic linkage disequilibrium (LD) difference was determined. Next, we assessed association for a variant at CRP and retinal vessel traits [central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE)] in a total of 24,132 subjects of East-Asian, South-Asian and European ancestry.Results:Serum CRP was associated with SNPs in/near APOE, CRP, HNF1A and LEPR (p-values ≤4.7×10-8) after meta-analysis of Singaporean populations. Using a candidate-SNP approach, we further replicated SNPs at 4 additional loci that had been recently identified to be associated with serum CRP (IL6R, GCKR, IL6 and IL1F10) (p-values ≤0.009), in the Singaporean datasets. SNPs from these 8 loci explained 4.05% of variance in serum CRP. Two SNPs (rs2847281 and rs6901250) were detected to be significant (p-value ≤0.036) but with opposite effect directions in the Singaporean populations as compared to original European studies. At these loci we did not detect significant inter-population LD differences. We further did not observe a significant association between CRP variant and CRVE or CRAE levels after meta-analysis of all Singaporean and European datasets (p-value >0.058).Conclusions:Common variants associated with serum CRP, first detected in primarily European studies, are also associated with CRP levels in East-Asian and South-Asian populations. We did not find a causal link between CRP and retinal measures of microvascular disease

Longitudinal analysis of the banking industry.

Banks in Singapore are faced with increased competition arising from the liberalisation of the financial service sector, and the advent of the Internet. This study seeks to provide understanding and insights to the phenomenon of electronic banking through the adoption of a multiple-case study design

Association results of index CRP loci (7–10) in Singaporean datasets.

<p>22 SNPs were genotyped or imputed and passed QC procedures in all 3 datasets and were combined in a meta-analysis (see Table S5 in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0067650#pone.0067650.s001" target="_blank">File S1</a> for full results). Significant results (p-value <0.05) in bold.</p><p>TAF: Test allele frequency. ^† Variants which were significant but not directionally consistent with previous European study (7).</p>*<p>Mean allele frequency from 3 SNP-chips used for the SP2 study. Q_pvalue <0.1 indicates between study heterogeneity.</p

Comparison of observed and expected association results for rs2794520 and CRVE in A) SP2, B) SiMES and C) SINDI datasets.

<p>Observed regression values presented in black and estimated values presented in gray. Regression models were adjusted for age and sex in SP2 and age, sex and population stratification (first 2 principal components in SiMES and first 3 principal components in SINDI only).</p

Clinical measures in SiMES, SP2 and SINDI datasets used in study.

*<p>Excluding 242 samples from SINDI, 190 samples from SiMES and 48 samples from SP2, respectively who had CRP values >10 mg/L.</p>†<p>hypertension defined as history of hypertension or SBP>140 mmHg or DBP>90 mmHg.</p>‡<p>diabetes defined as participants with a history of diabetes mellitus or fasting glucose levels ≥7.0 mmol/L in SP2 and HbA1c levels ≥6.5% in non-fasting blood samples and/or those with previous history in SiMES and SINDI.</p

Linear regression of rs2794520 with CRVE and CRAE traits in datasets used in the study.

<p>The test allele for rs2794520 was the G allele.</p><p>Estimated power: based on average predicted effect estimate (0.45 µm CRVE) from SiMES, SP2 and SINDI datasets (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0067650#pone-0067650-g001" target="_blank">Figure 1</a>) and a minor allele frequency of 0.40, at α = 0.05.</p

Analysis of clinically relevant variants from ancestrally diverse Asian genomes

Asian populations are under-represented in human genomics research. Here, we characterize clinically significant genetic variation in 9051 genomes representing East Asian, South Asian, and severely under-represented Austronesian-speaking Southeast Asian ancestries. We observe disparate genetic risk burden attributable to ancestry-specific recurrent variants and identify individuals with variants specific to ancestries discordant to their self-reported ethnicity, mostly due to cryptic admixture. About 27% of severe recessive disorder genes with appreciable carrier frequencies in Asians are missed by carrier screening panels, and we estimate 0.5% Asian couples at-risk of having an affected child. Prevalence of medically-actionable variant carriers is 3.4% and a further 1.6% harbour variants with potential for pathogenic classification upon additional clinical/experimental evidence. We profile 23 pharmacogenes with high-confidence gene-drug associations and find 22.4% of Asians at-risk of Centers for Disease Control and Prevention Tier 1 genetic conditions concurrently harbour pharmacogenetic variants with actionable phenotypes, highlighting the benefits of pre-emptive pharmacogenomics. Our findings illuminate the diversity in genetic disease epidemiology and opportunities for precision medicine for a large, diverse Asian population.</p

Large-Scale Whole-Genome Sequencing of Three Diverse Asian Populations in Singapore

Because of Singapore's unique history of immigration, whole-genome sequence analysis of 4,810 Singaporeans provides a snapshot of the genetic diversity across East, Southeast, and South Asia.</p