• 생물정신의학
• /
• 제13권3호
• /
• pp.170-177
• /
• 2006

Objectives : Disturbances of serotonergic system might be related to the possible mechanism of social phobia. This study was to investigate the association of serotonin transporter gene and social phobia. Methods : Sixty nine patients with social phobia(51 male(73.9%), mean age $35.17{\pm}11.89$ years) and seventy four normal controls(54 male(73.0%), mean age $33.46{\pm}9.63$ years) were tested for serotonin transporter gene-linked polymorphic region(5-HTTLPR) polymorphism. Additionally, patients were grouped into 46 generalized(GEN) and 23 nongeneralized(NGEN) subgroups and 5-HTTLPR polymorphism was compared with that of normal controls. The genotypes and allele frequencies of the 5-HTTLPR polymorphism between social phobia and the control group were compared. Genomic DNA was extracted from their blood and 5-HTTLPR polymorphisms were determined by using polymerase chain reaction. Results : Significant association was observed between the S(ss) genotype and social phobia, by functional classification(p=.010). In allele frequency analysis, a significant association was also observed between the short allele and social phobia(p=.030). A significant associations between S genotype and each subgroup were observed(GEN p=.045 ; NGEN p=.033), but there were no differences in allele frequency. And, no differences in genotype and allele distribution between two subgroups were found. Conclusion : The results in our Korean sample suggest that S genotype of 5-HTTLPR may be associated with social phobia and s allele may be an important genetic factor that activates social phobic symptoms. But, further studies including large number of samples are necessary to elucidate these present findings.

• 응용통계연구
• /
• 제23권6호
• /
• pp.1103-1113
• /
• 2010

광범위하게 사용되는 가족자료에 근거한 연관성 검정법 FBAT를 형제 전달 불균형 연관성 검정법 S-TDT와 비교하였고, 특히 형제간의 공분산을 고려한 분산추정량을 사용한 수정 S-TDT로써 유전연관성의 정도가 다른 가족자료가 검정통계량값으로 구분될 수가 있다. 모의실험으로 세 검정법을 비교한 결과, 형제의 표현형 자료가 서로 독립이 아닌 경우에 세 검정법 모두의 제 1종 오류가 정해진 유의수준보다 커지며, 또한 FBAT의 검정력이 S-TDT와 수정 S-TDT의 검정력에 미치지 못한다. FBAT 검정법에서 가정하는 조건이 검정법의 효율성에 미치는 영향을 더욱 심도있게 평가하는 연구가 요구된다.

• Journal of Korean Neurosurgical Society
• /
• 제61권1호
• /
• pp.66-74
• /
• 2018

Objective : The aim of this study was to identify the susceptibility genes responsible for lumbar spondylosis (LS) in Korean patients. Methods : Data from 1427 subjects were made available for radiographic grading and genome wide association studies (GWAS) analysis. Lateral lumbar spine radiographs were obtained and the various degrees of degenerative change were semi-quantitatively scored. A pilot GWAS was performed using the AffymetrixGenome-Wide Human single-nucleotide polymorphisms (SNPs), 500K array. A total of 352228 SNPs were analyzed and the association between the SNPs and case-control status was analyzed by stepwise logistic regression analyses. Results : The top 100 SNPs with a cutoff p-value of less than $3.7{\times}10^{-4}$ were selected for joint space narrowing, while a cutoff p-value of $6.0{\times}10^{-4}$ was applied to osteophytes and the Kellgren-Lawrence (K-L) osteoarthritis grade. The SNPs with the strongest effect on disc space narrowing, osteophytes, and K-L grade were serine incorporator 1 (rs155467, odds ratio [OR]=17.58, $p=1.6{\times}10^{-4}$), stromal interaction molecule 2 (STIM1, rs210781, OR=5.53, $p=5{\times}10^{-4}$), and transient receptor potential cation channel, subfamily C (rs11224760, OR=3.99, $p=4.8{\times}10^{-4}$), respectively. Leucine-rich repeat-containing G protein-coupled receptor 4 was significantly associated with both disc space narrowing and osteophytes (rs1979400, OR=2.01, $p=1.1{\times}10^{-4}$ for disc space narrowing, OR=1.79, $p=3{\times}10^{-4}$ for osteophytes), while zinc finger and BTB domain containing 7C was significantly and negatively associated with both osteophytes and a K-L grade >2 (rs12457004,OR=0.25, $p=5.8{\times}10^{-4}$ and OR=0.27, $p=5.3{\times}10^{-4}$, respectively). Conclusion : We identified SNPs that potentially contribute to the pathogenesis of LS. This is the first report of a GWAS in an Asian population.

• Asian-Australasian Journal of Animal Sciences
• /
• 제27권9호
• /
• pp.1219-1227
• /
• 2014

A whole genome association (WGA) study was carried out to find quantitative trait loci (QTL) for sensory evaluation traits in Hanwoo. Carcass samples of 250 Hanwoo steers were collected from National Agricultural Cooperative Livestock Research Institute, Ansung, Gyeonggi province, Korea, between 2011 and 2012 and genotyped with the Affymetrix Bovine Axiom Array 640K single nucleotide polymorphism (SNP) chip. Among the SNPs in the chip, a total of 322,160 SNPs were chosen after quality control tests. After adjusting for the effects of age, slaughter-year-season, and polygenic effects using genome relationship matrix, the corrected phenotypes for the sensory evaluation measurements were regressed on each SNP using a simple linear regression additive based model. A total of 1,631 SNPs were detected for color, aroma, tenderness, juiciness and palatability at 0.1% comparison-wise level. Among the significant SNPs, the best set of 52 SNP markers were chosen using a forward regression procedure at 0.05 level, among which the sets of 8, 14, 11, 10, and 9 SNPs were determined for the respectively sensory evaluation traits. The sets of significant SNPs explained 18% to 31% of phenotypic variance. Three SNPs were pleiotropic, i.e. AX-26703353 and AX-26742891 that were located at 101 and 110 Mb of BTA6, respectively, influencing tenderness, juiciness and palatability, while AX-18624743 at 3 Mb of BTA10 affected tenderness and palatability. Our results suggest that some QTL for sensory measures are segregating in a Hanwoo steer population. Additional WGA studies on fatty acid and nutritional components as well as the sensory panels are in process to characterize genetic architecture of meat quality and palatability in Hanwoo.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권11호
• /
• pp.6411-6413
• /
• 2013

Adenocarcinoma of esophagus (AE) is a complex disease, affected by a variety of genetic and environmental factors. Much evidence has shown that the MutY glycosylase homologue (MUTYH) plays a key role in the pathogenesis of many cancers. However, there have been no reports on influence on AE in the Han Chinese population. The objective of this study was to investigate this issue. A gene-based association study was conducted using three single nucleotide polymorphisms(SNPs) reported in previous studies. The three SNPs (rs3219463, rs3219472, rs3219489) were genotyped in 207 unrelated AE patients and 249 healthy controls in a case-control study using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The results revealed that the genotype distribution of rs3219472 differed between the case and control groups (OR=1.66,95%CI=1.11-2.48, P=0.012), indicating that an association may exist between MUTYH and AE. These findings support a signifcant role for MUTYH in AE pathogenesis in the Han Chinese population.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
• /
• 제29권2호
• /
• pp.62-72
• /
• 2018

Objectives: The molecular mechanisms underlying attention-deficit hyperactivity disorder (ADHD) remain unclear. Therefore, this study aimed to identify the genetic susceptibility loci for ADHD in Korean children with ADHD. We performed a case-control and a family-based genome-wide association study (GWAS), as well as genome-wide quantitative trait locus (QTL) analyses, for two symptom traits. Methods: A total of 135 subjects (71 cases and 64 controls), for the case-control analysis, and 54 subjects (27 probands and 27 unaffected siblings), for the family-based analysis, were included. Results: The genome-wide QTL analysis identified four single nucleotide polymorphisms (SNPs) (rs7684645 near APELA, rs12538843 near YAE1D1 and POU6F2, rs11074258 near MCTP2, and rs34396552 near CIDEA) that were significantly associated with the number of inattention symptoms in ADHD. These SNPs showed possible association with ADHD in the family-based GWAS, and with hyperactivity-impulsivity in genome-wide QTL analyses. Moreover, association signals in the family-based QTL analysis for the number of inattention symptoms were clustered near genes IL10, IL19, SCL5A9, and SKINTL. Conclusion: We have identified four QTLs with genome-wide significance and several promising candidates that could potentially be associated with ADHD (CXCR4, UPF1, SETD5, NALCN-AS1, ERC1, SOX2-OT, FGFR2, ANO4, and TBL1XR1). Further replication studies with larger sample sizes are needed.

• Genomics & Informatics
• /
• 제12권4호
• /
• pp.187-194
• /
• 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.

• 한국수정란이식학회지
• /
• 제30권3호
• /
• pp.137-142
• /
• 2015

Cryopreservation of boar semen is continually researched in reproductive technologies and genetic resource banking in breed conservation. For evaluating the boar semen quality, sperm motility (MOT) is an important parameter because the movement of spermatozoa indicates active metabolism, membrane integrity and fertilizing capacity. Various researches have been trying to improve the quality of semen post-thawed in boar. Recently, polymorphism (g.158T>C) of phospholipase C zeta (PLCz) gene reported to be significant association with MOT. This study was conducted to evaluate the PLCz gene as a positional controlling for motility and kinematic characteristics of post-thawed boar semen. To results, The g.158 T>C SNP of PLCz was significantly associated with frozen semen motility and kinematic characteristics. g.158 T>C SNP was high significantly associated with MOT, VCL, VSL and VAP (p<0.0001, p=0.0002, p<0.0001 and p<0.0001, respectively). Therefore, we suggest that the intron region of the porcine PLCz, may be used as a molecular marker for Duroc boar post-thawed semen quality, although its functional effect was not defined yet. Whether the association is due to the candidate gene or not require further verification. Thus, it will be of interest to continue association studies in the regions surrounding those genes.

• Asian-Australasian Journal of Animal Sciences
• /
• 제32권5호
• /
• pp.607-613
• /
• 2019

Objective: Intramuscular fat (IMF) content plays an important role in meat quality. Identification of single nucleotide polymorphisms (SNPs) and genes related to pig IMF, especially using pig populations with high IMF content variation, can help to establish novel molecular breeding tools for optimizing IMF in pork and unveil the mechanisms that underlie fat metabolism. Methods: We collected muscle samples of 453 Chinese Lulai black pigs, measured IMF content by Soxhlet petroleum-ether extraction method, and genotyped genome-wide SNPs using GeneSeek Genomic Profiler Porcine HD BeadChip. Then a genome-wide association study was performed using a linear mixed model implemented in the GEMMA software. Results: A total of 43 SNPs were identified to be significantly associated with IMF content by the cutoff p<0.001. Among these significant SNPs, the greatest number of SNPs (n = 19) were detected on Chr.9, and two linkage disequilibrium blocks were formed among them. Additionally, 17 significant SNPs are mapped to previously reported quantitative trait loci (QTLs) of IMF and confirmed previous QTLs studies. Forty-two annotated genes centering these significant SNPs were obtained from Ensembl database. Overrepresentation test of pathways and gene ontology (GO) terms revealed some enriched reactome pathways and GO terms, which mainly involved regulation of basic material transport, energy metabolic process and signaling pathway. Conclusion: These findings improve our understanding of the genetic architecture of IMF content in pork and facilitate the follow-up study of fine-mapping genes that influence fat deposition in muscle.

• Nutrition Research and Practice
• /
• 제17권4호
• /
• pp.789-802
• /
• 2023

BACKGROUND/OBJECTIVES: Habitual coffee consumption was inversely associated with type 2 diabetes (T2D) and hyperglycemia in observational studies, but the causality of the association remains uncertain. This study tested a causal association of genetically predicted coffee consumption with T2D using the Mendelian randomization (MR) method. SUBJECTS/METHODS: We used five single-nucleotide polymorphisms (SNPs) as instrumental variables (IVs) associated with habitual coffee consumption in a previous genome-wide association study among Koreans. We analyzed the associations between IVs and T2D, fasting blood glucose (FBG), 2h-postprandial glucose (2h-PG), and glycated haemoglobin (HbA1C) levels. The MR results were further evaluated by standard sensitivity tests for possible pleiotropism. RESULTS: MR analysis revealed that increased genetically predicted coffee consumption was associated with a reduced prevalence of T2D; ORs per one-unit increment of log-transformed cup per day of coffee consumption ranged from 0.75 (0.62-0.90) for the weighted mode-based method to 0.79 (0.62-0.99) for Wald ratio estimator. We also used the inverse-variance-weighted method, weighted median-based method, MR-Egger method, and MR-PRESSO method. Similarly, genetically predicted coffee consumption was inversely associated with FBG and 2h-PG levels but not with HbA1c. Sensitivity measures gave similar results without evidence of pleiotropy. CONCLUSIONS: A genetic predisposition to habitual coffee consumption was inversely associated with T2D prevalence and lower levels of FBG and 2h-PG profiles. Our study warrants further exploration.