• Genomics & Informatics
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• v.9 no.1
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• pp.1-4
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• 2011

Genome-wide association (GWA) studies are the method of choice for discovering loci associated with common diseases. More than a thousand GWA studies have reported successful identification of statistically significant association signals in human genomes for a variety of complex diseases. In this review, I discuss some of the issues related to the future of GWA studies and their biomedical applications.

• Communications for Statistical Applications and Methods
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• v.16 no.6
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• pp.915-923
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• 2009

The gene which is related in the disease of the human has been searched among numerous genes in GWA(Genome-Wide Association) research. However, most current statistical methods used to detect gene-gene interactions in disease association studies cannot be easily applied to handle the whole genome association study(GWAS) due to heavy computing. Therefore SNPHarvester is developed to find the main gene group among numerous genes. This research finds the superior gene groups which are related with the economic traits of the Korean beef cattle, not that of human, among sets of SNPs by using SNPHarvester, and also finds the superior genotypes which can enhance various qualities of Korean beef among SNP groups.

• Genomics & Informatics
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• v.8 no.3
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• pp.101-102
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• 2010

During the last decade, large community cohorts have been established by the Korea National Institutes of Health (KNIH), and enormous epidemiological and clinical data have been accumulated. Using these information and samples in the cohorts, KNIH set out to do a large-scale genome-wide association study (GWAS) in 2007, and the Korea Association REsource (KARE) consortium was launched to analyze the data to identify the underlying genetic risk factors of diseases and diverse health indexes, such as blood pressure, obesity, bone density, and blood biochemical traits. The consortium consisted of 6 research divisions, formed by 25 principal investigators in 19 organizations, including 18 universities, 2 institutes, and 1 company. Each division focused on one of the following subjects: the identification of genetic factors, the statistical analysis of gene-gene interactions, the genetic epidemiology of gene-environment interactions, copy number variation, the bioinformatics related to a GWAS, and a GWAS of nutrigenomics. In this special issue, the study results of the KARE consortium are provided as 9 articles. We hope that this special issue might encourage the genomics community to share data and scientists, including clinicians, to analyze the valuable Korean data of KARE.

• Asian-Australasian Journal of Animal Sciences
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• v.31 no.4
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• pp.473-479
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• 2018

Objective: The study was designed to perform a genome-wide association (GWA) and partitioning of genome using Illumina's PorcineSNP60 Beadchip in order to identify variants and determine the explained heritability for the total number of teats in Yorkshire pig. Methods: After screening with the following criteria: minor allele frequency, $MAF{\leq}0.01$; Hardy-Weinberg equilibrium, $HWE{\leq}0.000001$, a pair-wise genomic relationship matrix was produced using 42,953 single nucleotide polymorphisms (SNPs). A genome-wide mixed linear model-based association analysis (MLMA) was conducted. And for estimating the explained heritability with genome- or chromosome-wide SNPs the genetic relatedness estimation through maximum likelihood approach was used in our study. Results: The MLMA analysis and false discovery rate p-values identified three significant SNPs on two different chromosomes (rs81476910 and rs81405825 on SSC8; rs81332615 on SSC13) for total number of teats. Besides, we estimated that 30% of variance could be explained by all of the common SNPs on the autosomal chromosomes for the trait. The maximum amount of heritability obtained by partitioning the genome were $0.22{\pm}0.05$, $0.16{\pm}0.05$, $0.10{\pm}0.03$ and $0.08{\pm}0.03$ on SSC7, SSC13, SSC1, and SSC8, respectively. Of them, SSC7 explained the amount of estimated heritability along with a SNP (rs80805264) identified by genome-wide association studies at the empirical p value significance level of 2.35E-05 in our study. Interestingly, rs80805264 was found in a nearby quantitative trait loci (QTL) on SSC7 for the teat number trait as identified in a recent study. Moreover, all other significant SNPs were found within and/or close to some QTLs related to ovary weight, total number of born alive and age at puberty in pigs. Conclusion: The SNPs we identified unquestionably represent some of the important QTL regions as well as genes of interest in the genome for various physiological functions responsible for reproduction in pigs.

• Genomics & Informatics
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• v.19 no.4
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• pp.37.1-37.7
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• 2021

Genome-wide association studies (GWASs) facilitated the discovery of countless disease-associated variants. However, GWASs have mostly been conducted in European ancestry samples. Recent studies have reported that these European-based association results may reduce disease prediction accuracy when applied in non-Europeans. Therefore, previously reported variants should be validated in non-European populations to establish reliable scientific evidence for precision medicine. In this study, we validated known associations with type 2 diabetes (T2D) and related metabolic traits in 125,850 samples from a Korean population genotyped by the Korea Biobank Array (KBA). At the end of December 2020, there were 8,823 variants associated with glycemic traits, lipids, liver enzymes, and T2D in the GWAS catalog. Considering the availability of imputed datasets in the KBA genome data, publicly available East Asian T2D summary statistics, and the linkage disequilibrium among the variants (r² < 0.2), 2,900 independent variants were selected for further analysis. Among these, 1,837 variants (63.3%) were statistically significant (p ≤ 0.05). Most of the non-replicated variants (n = 1,063) showed insufficient statistical power and decreased minor allele frequencies compared with the replicated variants. Moreover, most of known variants showed <10% genetic heritability. These results could provide valuable scientific evidence for future study designs, the current power of GWASs, and future applications in precision medicine in the Korean population.

• BMB Reports
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• v.45 no.5
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• pp.305-310
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• 2012

Allergic diseases such as asthma, allergic rhinitis, and atopic dermatitis are heterogeneous diseases characterized by multiple symptoms and phenotypes. Recent advancements in genetic study enabled us to identify disease associated genetic factors. Numerous genome-wide association studies (GWAS) have revealed multiple associated loci for allergic diseases. However, the majority of previous studies have been conducted in populations of European ancestry. Moreover, the associations of single nucleotide polymorphisms (SNPs) with allergic diseases have not been studied amongst the large-scale general Korean population. Herein, we performed the replication study to validate the previous variants, known to be associated with allergic diseases, in the Korean population. In this study, we categorized three allergic related phenotypes, one allergy and two asthma related phenotypes, based on self-reports of physician diagnosis and their symptoms from 8,842 samples. As a result, we found nominally significant associations of 6 SNPs with at least one allergic related phenotype in the Korean population.

• Asian-Australasian Journal of Animal Sciences
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• v.28 no.6
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• pp.771-781
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• 2015

Thoroughbred, a relatively recent horse breed, is best known for its use in horse racing. Although myostatin (MSTN) variants have been reported to be highly associated with horse racing performance, the trait is more likely to be polygenic in nature. The purpose of this study was to identify genetic variants strongly associated with racing performance by using estimated breeding value (EBV) for race time as a phenotype. We conducted a two-stage genome-wide association study to search for genetic variants associated with the EBV. In the first stage of genome-wide association study, a relatively large number of markers (~54,000 single-nucleotide polymorphisms, SNPs) were evaluated in a small number of samples (240 horses). In the second stage, a relatively small number of markers identified to have large effects (170 SNPs) were evaluated in a much larger number of samples (1,156 horses). We also validated the SNPs related to MSTN known to have large effects on racing performance and found significant associations in the stage two analysis, but not in stage one. We identified 28 significant SNPs related to 17 genes. Among these, six genes have a function related to myogenesis and five genes are involved in muscle maintenance. To our knowledge, these genes are newly reported for the genetic association with racing performance of Thoroughbreds. It complements a recent horse genome-wide association studies of racing performance that identified other SNPs and genes as the most significant variants. These results will help to expand our knowledge of the polygenic nature of racing performance in Thoroughbreds.

• Genomics & Informatics
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• v.16 no.3
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• pp.59-64
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• 2018

Although pork quality traits are important commercially, genome-wide association studies (GWASs) have not well considered Landrace and Yorkshire pigs worldwide. Landrace and Yorkshire pigs are important pork-providing breeds. Although quantitative trait loci of pigs are well-developed, significant genes in GWASs of pigs in Korea must be studied. Through a GWAS using the PLINK program, study of the significant genes in Korean pigs was performed. We conducted a GWAS and surveyed the gene ontology (GO) terms associated with the backfat thickness (BF) trait of these pigs. We included the breed information (Yorkshire and Landrace pigs) as a covariate. The significant genes after false discovery rate (<0.01) correction were AFG1L, SCAI, RIMS1, and SPDEF. The major GO terms for the top 5% of genes were related to neuronal genes, cell morphogenesis and actin cytoskeleton organization. The neuronal genes were previously reported as being associated with backfat thickness. However, the genes in our results were novel, and they included ZNF280D, BAIAP2, LRTM2, GABRA5, PCDH15, HERC1, DTNBP1, SLIT2, TRAPPC9, NGFR, APBB2, RBPJ, and ABL2. These novel genes might have roles in important cellular and physiological functions related to BF accumulation. The genes related to cell morphogenesis were NOX4, MKLN1, ZNF280D, BAIAP2, DNAAF1, LRTM2, PCDH15, NGFR, RBPJ, MYH9, APBB2, DTNBP1, TRIM62, and SLIT2. The genes that belonged to actin cytoskeleton organization were MKLN1, BAIAP2, PCDH15, BCAS3, MYH9, DTNBP1, ABL2, ADD2, and SLIT2.

• Genomics & Informatics
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• v.12 no.4
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• pp.195-202
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• 2014

Metabolic syndrome (MetS) is a complex disorder related to insulin resistance, obesity, and inflammation. Genetic and environmental factors also contribute to the development of MetS, and through genome-wide association studies (GWASs), important susceptibility loci have been identified. However, GWASs focus more on individual single-nucleotide polymorphisms (SNPs), explaining only a small portion of genetic heritability. To overcome this limitation, pathway analyses are being applied to GWAS datasets. The aim of this study is to elucidate the biological pathways involved in the pathogenesis of MetS through pathway analysis. Cohort data from the Korea Associated Resource (KARE) was used for analysis, which include 8,842 individuals (age, $52.2{\pm}8.9years$ ; body mass index, $24.6{\pm}3.2kg/m^2$). A total of 312,121 autosomal SNPs were obtained after quality control. Pathway analysis was conducted using Meta-analysis Gene-Set Enrichment of Variant Associations (MAGENTA) to discover the biological pathways associated with MetS. In the discovery phase, SNPs from chromosome 12, including rs11066280, rs2074356, and rs12229654, were associated with MetS (p < $5{\times}10^{-6}$), and rs11066280 satisfied the Bonferroni-corrected cutoff (unadjusted p < $1.38{\times}10^{-7}$, Bonferroni-adjusted p < 0.05). Through pathway analysis, biological pathways, including electron carrier activity, signaling by platelet-derived growth factor (PDGF), the mitogen-activated protein kinase kinase kinase cascade, PDGF binding, peroxisome proliferator-activated receptor (PPAR) signaling, and DNA repair, were associated with MetS. Through pathway analysis of MetS, pathways related with PDGF, mitogen-activated protein kinase, and PPAR signaling, as well as nucleic acid binding, protein secretion, and DNA repair, were identified. Further studies will be needed to clarify the genetic pathogenesis leading to MetS.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2231-2235
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• 2015

Genome-wide association studies (GWASs) of the entire genome provide a systematic approach for revealing novel genetic susceptibility loci for breast cancer. However, genetic association studies have hitherto been primarily conducted in women of European ancestry. Therefofre we here performed a pilot GWAS with a single nucleotide polymorphism (SNP) array 5.0 platform from $Affymetrix^{(R)}$ that contains 443,813 SNPs to search for new genetic risk factors in 89 breast cancer cases and 46 healthy women of Indonesian ancestry. The case-control association of the GWAS finding set was evaluated using PLINK. The strengths of allelic and genotypic associations were assessed using logistic regression analysis and reported as odds ratios (ORs) and P values; P values less than $1.00{\times}10^{-8}$ and $5.00{\times}10^{-5}$ were required for significant association and suggestive association, respectively. After analyzing 292,887 SNPs, we recognized 11 chromosome loci that possessed suggestive associations with breast cancer risk. Of these, however, there were only four chromosome loci with identified genes: chromosome 2p.12 with the CTNNA2 gene [Odds ratio (OR)=1.20, 95% confidence interval (CI)=1.13-1.33, $P=1.08{\times}10^{-7}$]; chromosome 18p11.2 with the SOGA2 gene (OR=1.32, 95%CI=1.17-1.44, $P=6.88{\times}10^{-6}$); chromosome 5q14.1 with the SSBP2 gene (OR=1.22, 95%CI=1.11-1.34, $P=4.00{\times}10^{-5}$); and chromosome 9q31.1 with the TEX10 gene (OR=1.24, 95%CI=1.12-1.35, $P=4.68{\times}10^{-5}$). This study identified 11 chromosome loci which exhibited suggestive associations with the risk of breast cancer among Indonesian women.