• Genomics & Informatics
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• v.12 no.4
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• pp.187-194
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• 2014

Metabolic syndrome (METS) is a disorder of energy utilization and storage and increases the risk of developing cardiovascular disease and diabetes. To identify the genetic risk factors of METS, we carried out a genome-wide association study (GWAS) for 2,657 cases and 5,917 controls in Korean populations. As a result, we could identify 2 single nucleotide polymorphisms (SNPs) with genome-wide significance level p-values (< $5{\times}10^{-8}$), 8 SNPs with genome-wide suggestive p-values ($5{\times}10^{-8}{\leq}$ p < $1{\times}10^{-5}$), and 2 SNPs of more functional variants with borderline p-values ($5{\times}10^{-5}{\leq}$ p < $1{\times}10^{-4}$). On the other hand, the multiple correction criteria of conventional GWASs exclude false-positive loci, but simultaneously, they discard many true-positive loci. To reconsider the discarded true-positive loci, we attempted to include the functional variants (nonsynonymous SNPs [nsSNPs] and expression quantitative trait loci [eQTL]) among the top 5,000 SNPs based on the proportion of phenotypic variance explained by genotypic variance. In total, 159 eQTLs and 18 nsSNPs were presented in the top 5,000 SNPs. Although they should be replicated in other independent populations, 6 eQTLs and 2 nsSNP loci were located in the molecular pathways of LPL, APOA5, and CHRM2, which were the significant or suggestive loci in the METS GWAS. Conclusively, our approach using the conventional GWAS, reconsidering functional variants and pathway-based interpretation, suggests a useful method to understand the GWAS results of complex traits and can be expanded in other genomewide association studies.

• Genomics & Informatics
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• v.8 no.3
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• pp.131-137
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• 2010

Genome-wide association studies (GWASs) have greatly contributed to the identification of common variants responsible for numerous complex traits. There are, however, unavoidable limitations in detecting causal and/or rare variants for traits in this approach, which depends on an LD-based tagging SNP microarray chip. In an effort to detect potential casual and/or rare variants for complex traits, such as type 2 diabetes (T2D) and triglycerides (TGs), we conducted a targeted resequencing of loci identified by the Korea Association REsource (KARE) GWAS. The target regions for resequencing comprised whole exons, exon-intron boundaries, and regulatory regions of genes that appeared within 1 Mb of the GWA signal boundary. From 124 individuals selected in population-based cohorts, a total of 0.7 Mb target regions were captured by the NimbleGen sequence capture 385K array. Subsequent sequencing, carried out by the Roche 454 Genome Sequencer FLX, generated about 110,000 sequence reads per individual. Mapping of sequence reads to the human reference genome was performed using the SSAHA2 program. An average of 62.2% of total reads was mapped to targets with an average 22X-fold coverage. A total of 5,983 SNPs (average 846 SNPs per individual) were called and annotated by GATK software, with 96.5% accuracy that was estimated by comparison with Affymetrix 5.0 genotyped data in identical individuals. About 51% of total SNPs were singletons that can be considered possible rare variants in the population. Among SNPs that appeared in exons, which occupies about 20% of total SNPs, 304 nonsynonymous singletons were tested with Polyphen to predict the protein damage caused by mutation. In total, we were able to detect 9 and 6 potentially functional rare SNPs for T2D and triglycerides, respectively, evoking a further step of replication genotyping in independent populations to prove their bona fide relevance to traits.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.56 no.2
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• pp.212-220
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• 2023

Over the past 50 years, red sea bream Pagrus major has been selectively bred for more than 10 generations to improve its growth rate. However, the effect of genetic factors on growth under low- or non-fish meal diet is still unclear. Here, we analyzed 251 individuals randomly mating 21 females (dam) and 16 males (sire) to determine the difference in growth between non-fish meal (i.e., treatment group) and fish meal-based diet (i.e., control group), if any. The kinship coefficient between each group of individuals and their parents was estimated by the KING (Kinship-based Inference for GWASs) software package. The presumed parents of 74 individuals in the treatment group and 57 individuals in the control group could be effectively identified. Notably, one specific female was consistently related to high- rather than low-growth individuals in both groups. In addition, more than one parent in each group was related to either high- or low-growth individuals. Parents of both high-growth individuals in the treatment group and low-growth individuals in the control group were also identified. Although further study is required on various growth factors, this study suggests the possibility of selective breeding under non-fish meal diet.

• Nutrition Research and Practice
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• v.18 no.5
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• pp.721-745
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• 2024

BACKGROUND/OBJECTIVES: The high consumption of purine-rich meat is associated with hyperuricemia. However, there is limited evidence linking the consumption of red and processed meat to the genetic risk of hyperuricemia. We investigated the relationship between various combinations of red and processed meat consumption and the polygenic risk scores (PRSs) and the incidence of hyperuricemia in middle-aged Koreans. SUBJECTS/METHODS: We analyzed the data from 44,053 participants aged ≥40 years sourced from the Health Examinees (HEXA) cohort of the Korean Genome and Epidemiology Study (KoGES). Information regarding red and processed meat intake was obtained using a semiquantitative food frequency questionnaire (SQ-FFQ). We identified 69 independent single-nucleotide polymorphisms (SNPs) at uric acid-related loci using genome-wide association studies (GWASs) and clumping analyses. The individual PRS, which is the weighted sum of the effect size of each allele at the SNP, was calculated. We used multivariable Cox proportional hazards models adjusted for covariates to determine the relationship between red and processed meat intake and the PRS in the incidence of hyperuricemia. RESULTS: During an average follow-up period of 5 years, 2,556 patients with hyperuricemia were identified. For both men and women, the group with the highest red and processed meat intake and the highest PRS was positively associated with the development of hyperuricemia when compared with the group with the lowest red and processed meat intake and the lowest PRS (hazard ratio [HR], 2.72; 95% confidence interval [CI], 2.10-3.53; P < 0.0001; HR, 3.28; 95% CI, 2.45-4.40; P < 0.0001). CONCLUSION: Individuals at a high genetic risk for uric acid levels should moderate their consumption of red and processed meat to prevent hyperuricemia.

• Korean Journal of Schizophrenia Research
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• v.21 no.2
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• pp.43-50
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• 2018

Objectives : Genome-wide association studies (GWASs) and meta-analyses indicate that single-nucleotide polymorphisms (SNPs) in the a-1C subunit of the L-type voltage-dependent calcium channel (CACNA1C) gene increase the risk for schizophrenia and bipolar disorders (BDs). We investigated the association between the genetic variants on CACNA1C and schizophrenia and/or BDs in the Korean population. Methods : A total of 582 patients with schizophrenia, 336 patients with BDs consisting of 179 bipolar I disorder (BD-I) and 157 bipolar II disorder (BD-II), and 502 healthy controls were recruited. Based on previous results from other populations, three SNPs (rs10848635, rs1006737, and rs4765905) were selected and genotype-wise association was evaluated using logistic regression analysis under additive, dominant and recessive genetic models. Results : rs10848635 showed a significant association with schizophrenia (p=0.010), the combined schizophrenia and BD group (p=0.018), and the combined schizophrenia and BD-I group (p=0.011). The best fit model was dominant model for all of these phenotypes. The association remained significant after correction for multiple testing in schizophrenia and the combined schizophrenia and BD-I group. Conclusion : We identified a possible role of CACNA1C in the common susceptibility of schizophrenia and BD-I. However no association trend was observed for BD-II. Further efforts are needed to identify a specific phenotype associated with this gene crossing the current diagnostic categories.