Metabolic Syndrome Prediction Using Machine Learning Models with Genetic and Clinical Information from a Nonobese Healthy Population

The prevalence of metabolic syndrome (MS) in the nonobese population is not low. However, the identification and risk mitigation of MS are not easy in this population. We aimed to develop an MS prediction model using genetic and clinical factors of nonobese Koreans through machine learning methods. A prediction model for MS was designed for a nonobese population using clinical and genetic polymorphism information with five machine learning algorithms, including naïve Bayes classification (NB). The analysis was performed in two stages (training and test sets). Model A was designed with only clinical information (age, sex, body mass index, smoking status, alcohol consumption status, and exercise status), and for model B, genetic information (for 10 polymorphisms) was added to model A. Of the 7,502 nonobese participants, 647 (8.6%) had MS. In the test set analysis, for the maximum sensitivity criterion, NB showed the highest sensitivity: 0.38 for model A and 0.42 for model B. The specificity of NB was 0.79 for model A and 0.80 for model B. In a comparison of the performances of models A and B by NB, model B (area under the receiver operating characteristic curve [AUC] = 0.69, clinical and genetic information input) showed better performance than model A (AUC = 0.65, clinical information only input). We designed a prediction model for MS in a nonobese population using clinical and genetic information. With this model, we might convince nonobese MS individuals to undergo health checks and adopt behaviors associated with a preventive lifestyle

Genetic Polymorphisms Associated with the Neutrophil–Lymphocyte Ratio and Their Clinical Implications for Metabolic Risk Factors

Background: The neutrophil–lymphocyte ratio (NLR) is a valuable prognostic or predictive biomarker in various diseases, but the genetic factors that underlie the NLR have not been studied. We attempted to investigate polymorphisms related to NLR phenotype and analyze their ability to predict metabolic risks. Methods: A genome-wide association study was performed with log-transformed NLR using an Affymetrix Axiom™ KORV1.1-96 Array. Regression models for metabolic risk status were designed using the identified significant single-nucleotide polymorphisms (SNPs). Results: We identified four SNPs near the TMEM116, NAA25, and PTPN11 genes that were associated with the NLR. The top SNP associated with the log-transformed NLR was rs76181728 in TMEM116. A case–control study was performed to analyze the metabolic risks associated with each SNP after adjusting for age, sex, and body mass index (BMI). Three SNPs displayed significant odds ratios (ORs) for increased blood pressure and increased waist circumference. In the regression model for metabolic syndrome, rs76181728 showed a significant association (OR = 1.465, 95% confidence interval (CI) = 1.091–1.969, P = 0.011) after adjustment for the NLR phenotype. Conclusions: We identified four novel SNPs that are associated with the NLR in healthy Koreans. SNPs in relevant genes might therefore serve as biomarkers for metabolic risks

Effect of point defect and Mn concentration in time-resolved differential reflection in GaMnAs

We measured the transmission spectra and the time-resolved differential reflectivity Delta R in Ga1-xMnxAs for x <= 0.05 for several excitation wavelengths. The sign of Delta R in Ga1-xMnxAs (x=0.015 and x=0.03) was negative for photon energy larger than band gap at room temperature. The negative component of Delta R was explained by defect induced absorption and/or the reduction of exciton bleaching, rather than by the change in density of near band edge states associated with Mn incorporation. For Ga0.95Mn0.05As, absorption edge broadening was observed in the transmission spectra and the induced absorption effect was reduced by the screening of Mn local potential by photocarriers

Validation of the Utility of the Genetically Shared Regions of Chromosomes (GD-ICS) Measuring Method in Identifying Complicated Genetic Relatedness

Background: Relatives share more genomic regions than unrelated individuals, with closer relatives sharing more regions. This concept, paired with the increased availability of high- throughput single nucleotide polymorphism (SNP) genotyping technologies, has made it feasible to measure the shared chromosomal regions between individuals to assess their level of relation to each other. However, such techniques have remained in the conceptual rather than practical stages in terms of applying measures or indices. Recently, we developed an index called "genetic distance-based index of chromosomal sharing (GD-ICS)" utilizing large-scale SNP data from Korean family samples and demonstrated its potential for practical applications in kinship determination. In the current study, we present validation results from various real cases demonstrating the utility of this method in resolving complex familial relationships where information obtained from traditional short tandem repeats (STRs) or lineage markers is inconclusive. Methods: We obtained large-scale SNP data through microarray analysis from Korean individuals involving 13 kinship cases and calculated GD-ICS values using the method described in our previous study. Based on the GD-ICS reference constructed for Korean families, each disputed kinship was evaluated and validated using a combination of traditional STRs and lineage markers. Results: The cases comprised those A) that were found to be inconclusive using the traditional approach, B) for which it was difficult to apply traditional testing methods, and C) that were more conclusively resolved using the GD-ICS method. This method has overcome the limitations faced by traditional STRs in kinship testing, particularly in a paternity case with STR mutational events and in confirming distant kinship where the individual of interest is unavailable for testing. It has also been demonstrated to be effective in identifying various relationships without specific presumptions and in confirming a lack of genetic relatedness between individuals. Conclusion: This method has been proven effective in identifying familial relationships across diverse complex and practical scenarios. It is not only useful when traditional testing methods fail to provide conclusive results, but it also enhances the resolution of challenging kinship cases, which suggests its applicability in various types of practical casework.Y

Time-resolved differential reflection measurements on Ga1-xMnxAs

We measured the time-resolved differential reflectivity, Delta R, of Ga1-xMnxAs for x <= 0.05 for various excitation wavelengths and compared with the signals from semi-insulating GaAs substrates. The sign of AR from Ga1-xMnxAs (x = 0.015 and x = 0.03) was negative at 295 K for photon energies larger than bandgap, which was ascribed to defect-induced absorption or a reduction of exciton bleaching. We also discuss the screening of Mn alloy potential fluctuations by photocarriers in the time-resolved differential reflection of Ga1-xMnxAs

The association of genetic polymorphisms with nonalcoholic fatty liver disease in a longitudinal study

Background Several genetic variants are known to be associated with nonalcoholic fatty liver disease (NAFLD). We aimed to evaluate the longitudinal associations between genetic variants and NAFLD. Methods We performed a genome-wide association study (GWAS) in Korean individuals who underwent repeated health check-ups. NAFLD was defined by ultrasonography and exclusion of secondary causes. Results The subjects had a median age of 50.0 years, and 54.8% were male. The median follow-up duration was 39 months. Among the 3905 subjects without NAFLD at baseline, 874 (22.4%) subjects developed NAFLD, and among the 1818 subjects with NAFLD at baseline, NAFLD regressed in 336 (18.5%) subjects during the follow-up period. After adjusting for age, sex and body mass index, no single-nucleotide polymorphism (SNP) passed Bonferroni correction for genome-wide significance in the development or regression of NAFLD. Among the SNPs that passed the genome-wide suggestiveness threshold (p = 1E-04) in the discovery set in the GWAS, only 1 SNP (rs4906353) showed an association with the development of NAFLD, with marginal significance in the validation set (p-value, discovery set = 9.68E-5 and validation set = 0.00531). Conclusions This exploratory study suggests that longitudinal changes in NAFLD are not associated with genetic variants in the Korean population. These findings provide new insight into genetic mechanisms in the pathogenesis of NAFLD.The funding for this research was provided by Seoul National University Hospital Research Fund (grant 04–2018-0860), the Seoul National University Hospital had no role in the design of the study and collection, analysis, and interpretation of data and in writing of the manuscript

Genome-wide association study of coronary artery calcification in asymptomatic Korean populations.

Epidemiologic evidence indicates that the prevalence and severity of coronary artery disease vary depending on ethnicity. In this study, a genome-wide association study for coronary artery calcification (CAC) was performed in a Korean population-based sample of 400 subjects without prior coronary artery disease and replicated in another of 1,288 subjects. CAC score, as assessed by multi-detector computed tomography, was evaluated in volunteers for screening purposes as part of a routine health examination. CAC score greater than the 90th percentile across the age in each sex group was considered severe CAC. Single nucleotide polymorphisms (SNPs) associated with severe CAC after adjusting for age, sex, hypertension, and diabetes were investigated using the additive model of logistic regression. One SNP (rs10757272 in the intronic region of the CDKN2B-AS1 gene in chromosome 9p21.3) met Bonferroni correction in the discovery set (p = 7.55E-08) and was also significant in the validation set by TaqMan assay (p = 0.036). Subjects with rs10757272 were found to have an increased odds ratio (OR) of having severe CAC in multivariate logistic regression analysis after adjusting for age, sex, hypertension, and diabetes (adjusted OR 3.24 and 95% CI 2.11-4.97). In conclusion, SNP rs10757272 in chromosome 9p21.3 was associated with severe CAC based on age and sex in an asymptomatic community-based Korean population. Therefore, it was associated with promotion of coronary artery calcification in subclinical state

Genetic Determinants of Visit-to-Visit Lipid Variability: Genome-Wide Association Study in Statin-Naive Korean Population

Background and AimThere is a growing evidence that fluctuation in lipid profiles is important in cardiovascular outcomes. We aimed to identify single nucleotide polymorphism (SNP) variants associated with low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C) variability in statin-naive Korean subjects and evaluate their associations with coronary atherosclerosis. MethodsIn statin-naive subjects from Gene-Environment of Interaction and phenotype cohort, we performed genome-wide association studies of lipid variability; the discovery (first) and replication (second) sets included 4,287 and 1,086 subjects, respectively. Coronary artery calcium (CAC) score and degree of coronary artery stenosis were used as outcome measures. Cholesterol variability was determined by standard deviation and average successive variability, and significant coronary atherosclerosis was defined as CAC score >= 400 or coronary stenosis >= 70%. ResultsMean HDL-C and LDL-C level were 54 +/- 12 and 123 +/- 30 mg/dL in the first set and 53 +/- 12 and 126 +/- 29 mg/dL in the second set. APOA5 rs662799 and APOA5 rs2266788 were associated with LDL-C variability and PXDNL rs80056520, ALDH2 rs671, HECTD4 rs2074356, and CETP rs2303790 were SNPs associated for HDL-C variability. APOA5 rs662799 passed Bonferroni correction with p-value of 1.789 x 10(-9). Among the SNPs associated with cholesterol variability, rs80056520 and rs2266788 variants were associated with CACS >= 400 and coronary stenosis >= 70% and rs662799 variant was associated with coronary stenosis >= 70%. ConclusionTwo SNPs associated with LDL-C variability (APOA5 rs662799 and rs2266788) and one SNP associated with HDL-C variability (PXDNL rs80056520) were significantly associated with advanced coronary artery stenosis. Combining GWAS results with imaging parameters, our study may provide a deeper understanding of underlying pathogenic basis of the link between lipid variability and coronary atherosclerosis.N