• BMB Reports
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• 제47권6호
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• pp.348-353
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• 2014

The speed of sound (SOS) value is an indicator of bone mineral density (BMD). Previous genome-wide association (GWA) studies have identified a number of genes, whose variations may affect BMD levels. However, their biological implications have been elusive. We re-analyzed the GWA study dataset for the SOS values in skeletal sites of 4,659 Korean women, using a gene-set analysis software, GSA-SNP. We identified 10 common representative GO terms, and 17 candidate genes between these two traits (PGS < 0.05). Implication of these GO terms and genes in the bone mechanism is well supported by the literature survey. Interestingly, the significance levels of some member genes were inversely related, in several gene-sets that were shared between two skeletal sites. This implies that biological process, rather than SNP or gene, is the substantial unit of genetic association for SOS in bone. In conclusion, our findings may provide new insights into the biological mechanisms for BMD.

• Animal Bioscience
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• 제35권12호
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• pp.1827-1838
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• 2022

Objective: The semen quality of stallions including sperm motility is an important target of selection as it has a high level of individual variability. However, effects of the molecular architecture of the genome on the mechanisms of sperm formation and their preservation after thawing have been poorly investigated. Here, we conducted a genome-wide association study (GWAS) for the sperm motility of cryopreserved semen in stallions of various breeds. Methods: Semen samples were collected from the stallions of 23 horse breeds. The following semen characteristics were examined: progressive motility (PM), progressive motility after freezing (FPM), and the difference between PM and FPM. The respective DNA samples from these stallions were genotyped using Axiom Equine Genotyping Array. Results: We performed a GWAS search for single nucleotide polymorphism (SNP) markers and potential genes related to motility properties of frozen-thawed semen in the stallions of various breeds. As a result of the GWAS analysis, two SNP markers, rs1141327473 and rs1149048772, were identified that were associated with preservation of the frozen-thawed stallion sperm motility, the relevant putative candidate genes being NME/NM23 family member 8 (NME8), olfactory receptor family 2 subfamily AP member 1 (OR2AP1), and olfactory receptor family 6 subfamily C member 4 (OR6C4). Potential implications of effects of these genes on sperm motility are herein discussed. Conclusion: The GWAS results enabled us to localize novel SNPs and candidate genes for sperm motility in stallions. Implications of the study for horse breeding and genetics are a better understanding of genomic regions and candidate genes underlying stallion sperm quality, and improvement in horse reproduction and breeding techniques. The identified markers and genes for sperm cryotolerance and the respective genomic regions are promising candidates for further studying the biological processes in the formation and function of the stallion reproductive system.

• Asian-Australasian Journal of Animal Sciences
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• 제30권5호
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• pp.638-642
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• 2017

Objective: This study aimed to validate the statistical evidence from the genome-wide association study (GWAS) as true-positive and to better understand the effects of the glycophorin C (GYPC) gene on serum hemoglobin traits. Methods: Our initial GWAS revealed the presence of two single nucleotide polymorphisms (SNPs) (ASGA0069038 and ALGA0084612) for the hemoglobin concentration trait (HGB) in the 2.48 Mb region of SSC15. From this target region, GYPC was selected as a promising gene that associated with serum HGB traits in pigs. SNPs within the GYPC gene were detected by sequencing. Thereafter, we performed association analysis of the variant with the serum hemoglobin level in three pig populations. Results: We identified one SNP (g.29625094 T>C) in exon 3 of the GYPC gene. Statistical analysis showed a significant association of the SNP with the serum hemoglobin level on day 20 (p<0.05). By quantitative real-time polymerase chain reaction, the GYPC gene was expressed in eight different tissues. Conclusion: These results might improve our understanding of GYPC function and provide evidence for its association with serum hemoglobin traits in the pig. These results also indicate that the GYPC gene might serve as a useful marker in pig breeding programs.

• Genomics & Informatics
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• 제11권3호
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• pp.129-134
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• 2013

Orthostatic hypotension (OH) is defined by a 20-mm Hg difference of systolic blood pressure (dtSBP) and/or a 10-mm Hg difference of diastolic blood pressure (dtDBP) between supine and standing, and OH is associated with a failure of the cardiovascular reflex to maintain blood pressure on standing from a supine position. To understand the underlying genetic factors for OH traits (OH, dtSBP, and dtDBP), genome-wide association studies (GWASs) using 333,651 single nucleotide polymorphisms (SNPs) were conducted separately for two population-based cohorts, Ansung (n = 3,173) and Ansan (n = 3,255). We identified 8 SNPs (5 SNPs for dtSBP and 3 SNPs for dtDBP) that were repeatedly associated in both the Ansung and Ansan cohorts and had p-values of < $1{\times}10^{-5}$ in the meta-analysis. Unfortunately, the SNPs of the OH case control GWAS did not pass our p-value criteria. Four of 8 SNPs were located in the intergenic region of chromosome 2, and the nearest gene (CTNNA2) was located at 1 Mb of distance. CTNNA2 is a linker between cadherin adhesion receptors and the actin cytoskeleton and is essential for stabilizing dendritic spines in rodent hippocampal neurons. Although there is no report about the function in blood pressure regulation, hippocampal neurons interact primarily with the autonomic nervous system and might be related to OH. The remaining SNPs, rs7098785 of dtSBP trait and rs6892553, rs16887217, and rs4959677 of dtDBP trait were located in the PIK3AP1 intron, ACTBL2-3' flanking, STAR intron, and intergenic region, respectively, but there was no clear functional link to blood pressure regulation.

• Nutrition Research and Practice
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• 제10권1호
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• pp.115-124
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• 2016

BACKGROUND/OBJECTIVES: This is the first study to identify common genetic factors associated with the basal metabolic rate (BMR) and body mass index (BMI) in obese Korean women including overweight. This will be a basic study for future research of obese gene-BMR interaction. SUBJECTS/METHODS: The experimental design was 2 by 2 with variables of BMR and BMI. A genome-wide association study (GWAS) of single nucleotide polymorphisms (SNPs) was conducted in the overweight and obesity (BMI > $23kg/m^2$) compared to the normality, and in women with low BMR (< 1426.3 kcal/day) compared to high BMR. A total of 140 SNPs reached formal genome-wide statistical significance in this study (P < $1{\times}10^{-4}$). Surveys to estimate energy intake using 24-h recall method for three days and questionnaires for family history, a medical examination, and physical activities were conducted. RESULTS: We found that two NRG3 gene SNPs in the 10q23.1 chromosomal region were highly associated with BMR (rs10786764; $P=8.0{\times}10^{-7}$, rs1040675; $2.3{\times}10^{-6}$) and BMI (rs10786764; $P=2.5{\times}10^{-5}$, rs10786764; $6.57{\times}10^{-5}$). The other genes related to BMI (HSD52, TMA16, MARCH1, NRG1, NRXN3, and STK4) yielded P < $10{\times}10^{-4}$. Five new loci associated with BMR and BMI, including NRG3, OR8U8, BCL2L2-PABPN1, PABPN1, and SLC22A17 were identified in obese Korean women (P < $1{\times}10^{-4}$). In the questionnaire investigation, significant differences were found in the number of starvation periods per week, family history of stomach cancer, coffee intake, and trial of weight control in each group. CONCLUSION: We discovered several common BMR- and BMI-related genes using GWAS. Although most of these newly established loci were not previously associated with obesity, they may provide new insights into body weight regulation. Our findings of five common genes associated with BMR and BMI in Koreans will serve as a reference for replication and validation of future studies on the metabolic rate.

• Asian-Australasian Journal of Animal Sciences
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• 제26권11호
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• pp.1523-1528
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• 2013

To increase plumage color uniformity and understand the genetic background of Korean chickens, we performed a genome-wide association study of different plumage color in Korean native chickens. We analyzed 60K SNP chips on 279 chickens with GEMMA methods for GWAS and estimated the genetic heritability for plumage color. The estimated heritability suggests that plumage coloration is a polygenic trait. We found new loci associated with feather pigmentation at the genome-wide level and from the results infer that there are additional genetic effect for plumage color. The results will be used for selecting and breeding chicken for plumage color uniformity.

• Genomics & Informatics
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• 제10권2호
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• pp.99-105
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• 2012

Dyslipidemia, mainly characterized by high triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) levels, is an important etiological factor in the development of cardiovascular disease (CVD). Considering the relationship between childhood obesity and CVD risk, it would be worthwhile to evaluate whether previously identified lipid-related variants in adult subjects are associated with lipid variations in a childhood obesity study (n = 482). In an association analysis for 16 genome-wide association study (GWAS)-based candidate loci, we confirmed significant associations of a genetic predisposition to lipoprotein concentrations in a childhood obesity study. Having two loci (rs10503669 at LPL and rs16940212 at LIPC) that showed the strongest association with blood levels of TG and HDL-C, we calculated a genetic risk score (GRS), representing the sum of the risk alleles. It has been observed that increasing GRS is significantly associated with decreased HDL-C (effect size, $-1.13{\pm}0.07$) compared to single nucleotide polymorphism combinations without two risk variants. In addition, a positive correlation was observed between allelic dosage score and risk allele (rs10503669 at LPL) on high TG levels (effect size, $10.89{\pm}0.84$). These two loci yielded consistent associations in our previous meta-analysis. Taken together, our findings demonstrate that the genetic architecture of circulating lipid levels (TG and HDL-C) overlap to a large extent in childhood as well as in adulthood. Post-GWAS functional characterization of these variants is further required to elucidate their pathophysiological roles and biological mechanisms.

• Journal of Animal Science and Technology
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• 제64권5호
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• pp.830-841
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• 2022

Genetic analysis has great potential as a tool to differentiate between different species and breeds of livestock. In this study, the optimal combinations of single nucleotide polymorphism (SNP) markers for discriminating the Yeonsan Ogye chicken (Gallus gallus domesticus) breed were identified using high-density 600K SNP array data. In 3,904 individuals from 198 chicken breeds, SNP markers specific to the target population were discovered through a case-control genome-wide association study (GWAS) and filtered out based on the linkage disequilibrium blocks. Significant SNP markers were selected by feature selection applying two machine learning algorithms: Random Forest (RF) and AdaBoost (AB). Using a machine learning approach, the 38 (RF) and 43 (AB) optimal SNP marker combinations for the Yeonsan Ogye chicken population demonstrated 100% accuracy. Hence, the GWAS and machine learning models used in this study can be efficiently utilized to identify the optimal combination of markers for discriminating target populations using multiple SNP markers.

• Asian-Australasian Journal of Animal Sciences
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• 제32권4호
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• pp.494-500
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• 2019

Objective: Feed consumption contributes a large percentage for total production costs in the poultry industry. Detecting genes associated with feeding traits will be of benefit to improve our understanding of the molecular determinants for feed efficiency. The objective of this study was to identify candidate genes associated with feed conversion ratio (FCR) via genomewide association study (GWAS) using sequence data imputed from single nucleotide polymorphism (SNP) panel in a Chinese indigenous chicken population. Methods: A total of 435 Chinese indigenous chickens were phenotyped for FCR and were genotyped using a 600K SNP genotyping array. Twenty-four birds were selected for sequencing, and the 600K SNP panel data were imputed to whole sequence data with the 24 birds as the reference. The GWAS were performed with GEMMA software. Results: After quality control, 8,626,020 SNPs were used for sequence based GWAS, in which ten significant genomic regions were detected to be associated with FCR. Ten candidate genes, ubiquitin specific peptidase 44, leukotriene A4 hydrolase, ETS transcription factor, R-spondin 2, inhibitor of apoptosis protein 3, sosondowah ankyrin repeat domain family member D, calmodulin regulated spectrin associated protein family member 2, zinc finger and BTB domain containing 41, potassium sodium-activated channel subfamily T member 2, and member of RAS oncogene family were annotated. Several of them were within or near the reported FCR quantitative trait loci, and others were newly reported. Conclusion: Results from this study provide valuable prior information on chicken genomic breeding programs, and potentially improve our understanding of the molecular mechanism for feeding traits.

• Genomics & Informatics
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• 제19권4호
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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.