• 생물정신의학
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• 제17권2호
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• pp.65-69
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• 2010

Gene-environment interactions are important in pathogenesis of suicide or suicidal behavior. Twin and adoption studies and family studies show that genetic factors play a critical role in suicide or suicidal behavior. Given the strong association between serotonergic neurotransmission and suicide, recent molecular genetic studies have focused on polymorphisms of serotonin genes, especially on serotonin transporter and tryptophan hydroxylase genes. Some studies have revealed a significant interaction between s allele of the serotonin transporter gene and the risk of suicide attempt associated with childhood trauma. In addition, the polymorphism of brain-derived neurotrophic factor gene also may influence the effect of childhood trauma in relation to the risk of attempting suicide. Future studies should explore genetic and environmental factors in suicide or suicidal behavior and examine for gene and environment interaction.

• Asian-Australasian Journal of Animal Sciences
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• 제30권1호
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• pp.1-7
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• 2017

Objective: Three genome-wide association studies (GWAS) and a meta-analysis of GWAS were conducted to explore the genetic mechanisms underlying variation in pig teat number. Methods: We performed three GWAS and a meta-analysis for teat number on three pig populations, including a White Duroc${\times}$Erhualian $F_2$ resource population (n = 1,743), a Chinese Erhualian pig population (n = 320) and a Chinese Sutai pig population (n = 383). Results: We detected 24 single nucleotide polymorphisms (SNPs) that surpassed the genome-wide significant level on Sus Scrofa chromosomes (SSC) 1, 7, and 12 in the $F_2$ resource population, corresponding to four loci for pig teat number. We highlighted vertnin (VRTN) and lysine demethylase 6B (KDM6B) as two interesting candidate genes at the loci on SSC7 and SSC12. No significant associated SNPs were identified in the meta-analysis of GWAS. Conclusion: The results verified the complex genetic architecture of pig teat number. The causative variants for teat number may be different in the three populations

• Journal of the Korean Data and Information Science Society
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• 제25권5호
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• pp.1127-1135
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• 2014

Genome-wide association studies (GWAS) are designed to discover genetic variants such as single nucleotide polymorphisms (SNPs) that are associated with human complex traits. Although there is an increasing interest in the application of GWAS methodologies to population-based cohorts, many published GWAS have adopted a case-control design, which raise an issue related to a sampling bias of both case and control samples. Because of unequal selection probabilities between cases and controls, the samples are not representative of the population that they are purported to represent. Therefore, non-random sampling in case-control study can potentially lead to inconsistent and biased estimates of SNP-trait associations. In this paper, we proposed inverse-probability of sampling weights based on disease prevalence to eliminate a case-control sampling bias in estimation and testing for association between SNPs and quantitative traits. We apply the proposed method to a data from the Korea Association Resource project and show that the standard estimators applied to the weighted data yield unbiased estimates.

• Asian Pacific Journal of Cancer Prevention
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• 제13권12호
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• pp.6005-6010
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• 2012

Background: Nasopharyngeal carcinoma (NPC) is endemic in Southern Chinese and Southeast Asian populations. Geographical and ethnic clustering of the cancer is due to genetic, environmental, and lifestyle risk factors. This case-control study aimed to identify or confirm both genetic and non-genetic risk factors for NPC in one of the endemic countries, Malaysia. Materials and Methods: A panel of 768 single-nucleotide polymorphisms (SNPs) previously associated with various cancers and known non-genetic risk factors for NPC were selected and analyzed for their associations with NPC in a case-control study. Results: Statistical analysis identified 40 SNPs associated with NPC risk in our population, including 5 documented previously by genome-wide association studies (GWAS) and other case-control studies; the associations of the remaining 35 SNPs with NPC were novel. In addition, consistent with previous studies, exposure to occupational hazards, overconsumption of salt-cured foods, red meat, as well as low intake of fruits and vegetables were also associated with NPC risk. Conclusions: In short, this study confirmed and/or identified genetic, environmental and dietary risk factors associated with NPC susceptibility in a Southeast Asian population.

• Asian Pacific Journal of Cancer Prevention
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• 제15권22호
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• pp.9643-9647
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• 2014

Background: Several studies have been performed to investigate the association of the HER2 Ile655Val polymorphism and breast cancer risk. However, the results were inconsistent. To understand the precise relationship, a meta-analysis was here conducted. Materials and Methods: A search of PubMed conducted to investigate links between the HER2 Ile655Val polymorphism and breast cancer, identified a total of 32 studies, of which 29, including 14,926 cases and 15,768 controls, with odds ratios (ORs) with 95% confidence intervals were used to assess any association. Results: In the overall analysis, the HER2 Ile655Val polymorphism was associated with breast cancer in an additive genetic model (OR=1.136, 95% CI 1.043-1.239, p=0.004) and in a dominant genetic (OR=1.118, 95% CI 1.020-1.227, p=0.018), while no association was found in a recessive genetic model. On subgroup analysis, an association with breast cancer was noted in the additive genetic model (OR=1.111, 95% CI: 1.004-1.230, p=0.042) for the Caucasian subgroup. No significant associations were observed in Asians and Africans in any of the genetic models. Conclusions: In summary, our meta-analysis findings suggest that the HER2 Ile655Val polymorphism is marginally associated with breast cancer susceptibility in worldwide populations with additive and dominant models, but not a recessive model.

• Genomics & Informatics
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• 제16권4호
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• pp.39.1-39.3
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• 2018

The rapid increase in genetic dataset volume has demanded extensive adoption of biological knowledge to reduce the computational complexity, and the biological pathway is one well-known source of such knowledge. In this regard, we have introduced a novel statistical method that enables the pathway-based association study of large-scale genetic dataset-namely, PHARAOH. However, researcher-level application of the PHARAOH method has been limited by a lack of generally used file formats and the absence of various quality control options that are essential to practical analysis. In order to overcome these limitations, we introduce our integration of the PHARAOH method into our recently developed all-in-one workbench. The proposed new PHARAOH program not only supports various de facto standard genetic data formats but also provides many quality control measures and filters based on those measures. We expect that our updated PHARAOH provides advanced accessibility of the pathway-level analysis of large-scale genetic datasets to researchers.

• Journal of Genetic Medicine
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• 제6권2호
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• pp.121-130
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• 2009

자궁내막증의 유전 소인을 감안하였을 때 관련 유전자 다형성 조사는 매우 중요한 의미를 갖는다. 현재까지 약 30여개의 한국인을 대상으로 한 결과를 조사하여 자궁내막증과 특정 유전자내 다형성과의 연관성을 파악하고자 하였다. 가장 의미있는 유전자 다형성은 한국인 자궁내막증 환자에서의 GSTT1, AhRR, ER-alpha, VEGF, AHSG, 그리고TNF-alpha 유전자 다형성이다. 다만 결과가 부분적으로 상충되기도 하여 추가 연구을 통해 결과 재현성을 증명해야 할 것으로 사료된다. 마지막으로 자궁내막증을 대상으로 유전자 연구에서의 추후 연구 방향을 제시하고자 한다.

• Toxicological Research
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• 제35권4호
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• pp.319-330
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• 2019

Adverse drug reactions (ADRs) constitute key factors in determining successful medication therapy in clinical situations. Integrative analysis of electronic medical record (EMR) data and use of proper analytical tools are requisite to conduct retrospective surveillance of clinical decisions on medications. Thus, we suggest that electronic medical recording and human genetic databases are considered together in future directions of pharmacovigilance. We analyzed EMR-based ADR studies indexed on PubMed during the period from 2005 to 2017 and retrospectively acquired 1161 (29.6%) articles describing drug-induced adverse reactions (e.g., liver, kidney, nervous system, immune system, and inflammatory responses). Of them, only 102 (8.79%) articles contained useful information to detect or predict ADRs in the context of clinical medication alerts. Since insufficiency of EMR datasets and their improper analyses may provide false warnings on clinical decision, efforts should be made to overcome possible problems on data-mining, analysis, statistics, and standardization. Thus, we address the characteristics and limitations on retrospective EMR database studies in hospital settings. Since gene expression and genetic variations among individuals impact ADRs, pharmacokinetics, and pharmacodynamics, appropriate paths for pharmacovigilance may be optimized using suitable databases available in public domain (e.g., genome-wide association studies (GWAS), non-coding RNAs, microRNAs, proteomics, and genetic variations), novel targets, and biomarkers. These efforts with new validated biomarker analyses would be of help to repurpose clinical and translational research infrastructure and ultimately future personalized therapy considering ADRs.

• Asian Pacific Journal of Cancer Prevention
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• 제16권2호
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• pp.713-718
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• 2015

Background: A number of association studies have been carried out to investigate the relationship between genetic polymorphisms in DNA repair genes and response to radiotherapy-based multimodality treatment of patients with rectal cancer. However, their conclusions were inconsistent. The objective of the present study was to assess the role of DNA repair gene genetic polymorphisms in predicting genetic biomarkers of the response in rectal cancer patients treated with neoadjuvant chemoradiation. Materials and Methods: Studies were retrieved by searching the PubMed database, Cochrane Library, Embase, and ISI Web of Knowledge. We conducted a meta-analysis to evaluate the association between genetic polymorphisms and the response in rectal cancer treated with neoadjuvant chemoradiation by checking odds ratios (ORs) and 95% confidence intervals (CIs). Results: Data were extracted from 5 clinical studies for this meta-analysis. The results showed that XRCC1 RS25487, XRCC1 RS179978, XRCC3 RS861539, ERCC1 RS11615 and ERCC2 RS13181 were not associated with the response in the radiotherapy-based multimodality treatment of patients with rectal cancer (p>0.05). Conclusions: This study shows that DNA repair gene common genetic polymorphisms are not significantly correlated with the radiotherapy-based multimodality treatment in rectal cancer patients.

• 대한치매학회지
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• 제17권4호
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• pp.131-136
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• 2018

Alzheimer's disease (AD) related genes have been elucidated by advanced genetic techniques. Familial autosomal dominant AD genes founded by linkage analyses are APP, PSEN1, PSEN2, ABCA7, and SORL1. Genome-wide association studies have found risk genes such as ABCA7, BIN1, CASS4, CD33, CD2AP, CELF1, CLU, CR1, DSG2, EPHA1, FERMT2, HLA-DRB5-HLA-DRB1, INPP5D, MEF2C, MS4A6A/MS4A4E, NME8, PICALM, PTK2B, SLC24A4, SORL1, and ZCWPW1. ABCA7, SORL1, TREM2, and APOE are proved to have high odds ratio (>2) in risk of AD using next generation sequencing studies. Thanks to the promising genetic techniques such as CRISPR-CAS9 and single-cell RNA sequencing opened a new era in genetics. CRISPR-CAS9 can directly link genetic knowledge to future treatment. Single-cell RNA sequencing are providing useful information on cell biology and pathogenesis of diverse diseases.