Robust imputation method for missing values in microarray data

<p>Abstract</p> <p>Background</p> <p>When analyzing microarray gene expression data, missing values are often encountered. Most multivariate statistical methods proposed for microarray data analysis cannot be applied when the data have missing values. Numerous imputation algorithms have been proposed to estimate the missing values. In this study, we develop a robust least squares estimation with principal components (RLSP) method by extending the local least square imputation (LLSimpute) method. The basic idea of our method is to employ quantile regression to estimate the missing values, using the estimated principal components of a selected set of similar genes.</p> <p>Results</p> <p>Using the normalized root mean squares error, the performance of the proposed method was evaluated and compared with other previously proposed imputation methods. The proposed RLSP method clearly outperformed the weighted <it>k</it>-nearest neighbors imputation (kNNimpute) method and LLSimpute method, and showed competitive results with Bayesian principal component analysis (BPCA) method.</p> <p>Conclusion</p> <p>Adapting the principal components of the selected genes and employing the quantile regression model improved the robustness and accuracy of missing value imputation. Thus, the proposed RLSP method is, according to our empirical studies, more robust and accurate than the widely used kNNimpute and LLSimpute methods.</p

Replication of genome-wide association studies on asthma and allergic diseases in Korean adult population

Allergic diseases such as asthma, allergic rhinitis, and atopicdermatitis are heterogeneous diseases characterized by multiplesymptoms and phenotypes. Recent advancements in geneticstudy enabled us to identify disease associated genetic factors.Numerous genome-wide association studies (GWAS) have revealedmultiple associated loci for allergic diseases. However,the majority of previous studies have been conducted in populationsof European ancestry. Moreover, the associations of singlenucleotide polymorphisms (SNPs) with allergic diseaseshave not been studied amongst the large-scale general Koreanpopulation. Herein, we performed the replication study to validatethe previous variants, known to be associated with allergicdiseases, in the Korean population. In this study, we categorizedthree allergic related phenotypes, one allergy and two asthmarelated phenotypes, based on self-reports of physician diagnosisand their symptoms from 8,842 samples. As a result, we foundnominally significant associations of 6 SNPs with at least one allergicrelated phenotype in the Korean population. [BMB reports2012; 45(5): 305-310

Smoking and Genetic Risk Variation Across Populations of E uropean, A sian, and A frican A merican Ancestry—A Meta‐Analysis of Chromosome 15q25

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91126/1/gepi21627.pd

Associations of Variants in CHRNA5/A3/B4 Gene Cluster with Smoking Behaviors in a Korean Population

Multiple genome-wide and targeted association studies reveal a significant association of variants in the CHRNA5-CHRNA3-CHRNB4 (CHRNA5/A3/B4) gene cluster on chromosome 15 with nicotine dependence. The subjects examined in most of these studies had a European origin. However, considering the distinct linkage disequilibrium patterns in European and other ethnic populations, it would be of tremendous interest to determine whether such associations could be replicated in populations of other ethnicities, such as Asians. In this study, we performed comprehensive association and interaction analyses for 32 single-nucleotide polymorphisms (SNPs) in CHRNA5/A3/B4 with smoking initiation (SI), smoking quantity (SQ), and smoking cessation (SC) in a Korean sample (N = 8,842). We found nominally significant associations of 7 SNPs with at least one smoking-related phenotype in the total sample (SI: P = 0.015∼0.023; SQ: P = 0.008∼0.028; SC: P = 0.018∼0.047) and the male sample (SI: P = 0.001∼0.023; SQ: P = 0.001∼0.046; SC: P = 0.01). A spectrum of haplotypes formed by three consecutive SNPs located between rs16969948 in CHRNA5 and rs6495316 in the intergenic region downstream from the 5′ end of CHRNB4 was associated with these three smoking-related phenotypes in both the total and the male sample. Notably, associations of these variants and haplotypes with SC appear to be much weaker than those with SI and SQ. In addition, we performed an interaction analysis of SNPs within the cluster using the generalized multifactor dimensionality reduction method and found a significant interaction of SNPs rs7163730 in LOC123688, rs6495308 in CHRNA3, and rs7166158, rs8043123, and rs11072793 in the intergenic region downstream from the 5′ end of CHRNB4 to be influencing SI in the male sample. Considering that fewer than 5% of the female participants were smokers, we did not perform any analysis on female subjects specifically. Together, our detected associations of variants in the CHRNA5/A3/B4 cluster with SI, SQ, and SC in the Korean smoker samples provide strong evidence for the contribution of this cluster to the etiology of SI, ND, and SC in this Asian population

East Asian specific asthma associated variants were discovered via exome-sequencing

Rapid development in sequencing technology enabled us study a near complete catalogue of variants in human genome. We performed whole-exome sequencing to identify functional variants responsible for severe asthma in Korean population. We identified 10 variants of 6 candidate asthma genes (P &lt; 10(-5)) comprising GPR88, AGTRAP, GTP2IRD1, KANK1, DNHD1, and DCUN1D2. Our study provides possible new therapeutic targets for asthma.N

Role of an unclassified Lachnospiraceae in the pathogenesis of type 2 diabetes: a longitudinal study of the urine microbiome and metabolites

Recent investigations have revealed that the human microbiome plays an essential role in the occurrence of type 2 diabetes (T2D). However, despite the importance of understanding the involvement of the microbiota throughout the body in T2D, most studies have focused specifically on the intestinal microbiota. Extracellular vesicles (EVs) have been recently found to provide important evidence regarding the mechanisms of T2D pathogenesis, as they act as key messengers between intestinal microorganisms and the host. Herein, we explored microorganisms potentially associated with T2D by tracking changes in microbiota-derived EVs from patient urine samples collected three times over four years. Mendelian randomization analysis was conducted to evaluate the causal relationships among microbial organisms, metabolites, and clinical measurements to provide a comprehensive view of how microbiota can influence T2D. We also analyzed EV-derived metagenomic (N = 393), clinical (N = 5032), genomic (N = 8842), and metabolite (N = 574) data from a prospective longitudinal Korean community-based cohort. Our data revealed that GU174097_g, an unclassified Lachnospiraceae, was associated with T2D (beta = -189.13; p = 0.00006), and it was associated with the ketone bodies acetoacetate and 3-hydroxybutyrate (r = -0.0938 and -0.0829, respectively; p = 0.0022 and 0.0069, respectively). Furthermore, a causal relationship was identified between acetoacetate and HbA1c levels (beta = 0.0002; p = 0.0154). GU174097_g reduced ketone body levels, thus decreasing HbA1c levels and the risk of T2D. Taken together, our findings indicate that GU174097_g may lower the risk of T2D by reducing ketone body levels. Diabetes: a little help from the microbiome A microbe that may help protect against type II diabetes has been detected by examining extracellular vesicles (EVs), tiny membrane-wrapped packages secreted by human cells and by the bacteria making up the microbiome. Examining EVs allows researchers to sample microbial populations other than the intensively studied intestinal microbiome. Sungho Won, Seoul National University, and Geum-Sook Hwang, Korea Basic Science Institute, Seoul, and coworkers studied the microbial EVs in urine samples collected from South Korean subjects over four years. They identified a previously unclassified bacterial species in the family Lachnospiraceae that was associated with lower risk of developing type II diabetes. Further investigation showed that these bacteria may break down ketone bodies, metabolic byproducts that signal disrupted sugar metabolism leading to diabetes. These results contribute to understanding how the microbiome contributes to metabolic health and disease.N

Heritability Analyses Uncover Shared Genetic Effects of Lung Function and Change over Time

Genetic influence on lung functions has been identified in previous studies; however, the relative longitudinal effects of genetic factors and their interactions with smoking on lung function remain unclear. Here, we identified the longitudinal effects of genetic variants on lung function by determining single nucleotide polymorphism (SNP) heritability and genetic correlations, and by analyzing interactions with smoking. Subject-specific means and annual change rates were calculated for eight spirometric measures obtained from 6622 Korean adults aged 40-69 years every two years for 14 years, and their heritabilities were estimated separately. Statistically significant (p &lt; 0.05) heritability for the subject-specific means of all spirometric measures (8 similar to 32%) and change rates of forced expiratory volume in 1 s to forced vital capacity ratio (FEV1/FVC; 16%) and post-bronchodilator FEV1/FVC (17%) were detected. Significant genetic correlations of the change rate with the subject-specific mean were observed for FEV1/FVC (rho(g) = 0.64) and post-bronchodilator FEV1/FVC (rho(g) = 0.47). Furthermore, post-bronchodilator FEV1/FVC showed significant heritability of SNP-by-smoking interaction (hGXS2 = 0.4) for the annual change rate. The GWAS also detected genome-wide significant SNPs for FEV1 (rs4793538), FEV1/FVC (rs2704589, rs62201158, and rs9391733), and post-bronchodilator FEV1/FVC (rs2445936). We found statistically significant evidence of heritability role on the change in lung function, and this was shared with the effects on cross-sectional measurements. We also found some evidence of interaction with smoking for the change of lung function.N