• Genomics & Informatics
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• v.19 no.4
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• pp.36.1-36.11
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• 2021

Predicting individual traits and diseases from genetic variants is critical to fulfilling the promise of personalized medicine. The genetic variants from genome-wide association studies (GWAS), including variants well below GWAS significance, can be aggregated into highly significant predictions across a wide range of complex traits and diseases. The recent arrival of large-sample public biobanks enables highly accurate polygenic predictions based on genetic variants across the whole genome. Various statistical methodologies and diverse computational tools have been introduced and developed to computed the polygenic risk score (PRS) more accurately. However, many researchers utilize PRS tools without a thorough understanding of the underlying model and how to specify the parameters for the best performance. It is advantageous to study the statistical models implemented in computational tools for PRS estimation and the formulas of parameters to be specified. Here, we review a variety of recent statistical methodologies and computational tools for PRS computation.

• Genomics & Informatics
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• v.10 no.2
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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 Korean Biological Nursing Science
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• v.25 no.1
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• pp.73-85
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• 2023

Purpose: This study focused on identifying the interaction effects of genetic and lifestyle-environmental factors on the development of type 2 diabetes mellitus (T2D). Methods: Study subjects were selected from the Korean Genome and Epidemiology Study (KoGES) from 2001 to 2014. Data on genetic variations, anthropometric measurements, biochemical data, and seven lifestyle factors (diet, physical activity, alcohol drinking, smoking, sleep, depression, and stress) were obtained from 4,836 Koreans aged between 40 and 59 years, including those with T2D at baseline (n = 1,209), newly developed T2D (n= 1,298) and verified controls (n = 3,538). The genetic risk score (GRS) was calculated by using 11 single-nucleotide polymorphisms (SNPs) related to T2D development and the second quartile was used as the reference category. A Cox proportional hazards regression model was used to evaluate the associations of GRS and lifestyle factors with T2D risk, controlling for covariates. Results: Multivariate regression analysis revealed that GRS was the strongest risk factor for T2D, and body mass index (BMI), smoking, drinking, and spicy food preference also increased the risk. Lifestyle/environmental factors that showed significant interactions with GRS were BMI, current smoking, current drinking, fatty food preference, and spicy food preference. Conclusions: Interactions between genetic factors and lifestyle/environmental factors were associated with an increased risk of T2D. The results will be useful to provide a new perspective on genetic profiling for the earlier detection of T2D risk and clues for personalized interventions, which might be more effective prevention strategies or therapies in individuals with a genetic predisposition to T2D.

• Korean Journal of Schizophrenia Research
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• v.23 no.2
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• pp.65-70
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• 2020

Objectives: This study aimed to explore whether common genetic variants that confer the risk of schizophrenia have similar effects between Korean and European ancestries using the polygenic risk score (PRS) analysis. Methods: Study subjects included 713 Korean patients with schizophrenia and 497 healthy controls. The Korea Biobank array was used for genotyping. Summary statistics of the most recent genome-wide association study (GWAS) of the European population were used as baseline data to calculate PRS. Logistic regression was conducted to determine the association between calculated PRS of European patients with schizophrenia and clinical diagnosis of schizophrenia in the Korean population. Results: Schizophrenia PRS was significantly higher in patients with schizophrenia than in healthy controls. The PRS at the p-value threshold of 0.5 best explained the variance of schizophrenia (R²=0.028, p=4.4×10^-6). The association was significant after adjusting for age and sex (odds ratio=1.34, 95% confidence interval=1.19-1.51, p=1.1×10^-6). The pattern of the association remained similar across different p-value thresholds (0.01-1). Conclusion: Schizophrenia PRS calculated using the European GWAS data showed a significant association with the clinical diagnosis of schizophrenia in the Korean population. Results suggest overlapping genetic risk variants between the two populations.

• Journal of Genetic Medicine
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• v.18 no.1
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• pp.38-43
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• 2021

Purpose: Demand for genetic counseling on cancer predisposition syndrome is increasing. We evaluated the psychological effect on counselees after genetic counseling at a clinic in a single center. Materials and Methods: We surveyed a total of 72 enrolled participants who visited a genetic counseling clinic at the Samsung Medical Center (SMC). The initial survey was conducted before the first genetic counseling session, and the second survey was conducted after the second genetic counseling session. A total of 43 participants completed both the initial and second surveys. Results: The initial survey of 72 participants indicated higher feelings of guilt in the group with religion, higher depression and anxiety in the group with a diagnosis of self, and higher anxiety in the group on self-referral to the genetic counseling clinic. In the completed survey of 43 participants, overall decreased depression was observed after the second genetic counseling session (P=0.013). Risk perception and anxiety decreased in the group diagnosed with benign variant/variant of uncertain significance (BV/VUS, 25/3) and increased in the group diagnosed with pathogenic variant (PV, 15). Risk perception and anxiety differed between the BV/VUS and PV groups (P<0.001 and P=0.03, respectively). Conclusion: The genetic counseling clinic at the SMC was effective in ameliorating the depression score. Assessment of survey results revealed different depression scores, feelings of guilt and anxiety, and different effects of the genetic counseling clinic, depending on the subgroups. Understanding the needs and psychological characteristics of different groups is necessary for improving genetic counseling services.

• Asian Oncology Nursing
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• v.10 no.2
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• pp.240-246
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• 2010

Purpose: Advancing genetic knowledge for oncology nurses is especially important in Korea because physicians have launched to incorporate genetic risk assessment and genetic testing into their practice. The purpose of this paper was to identify the effect of the first academic cancer genetic risk assessment and counseling course for Korean nurses. Methods: Thirty-five nurses were recruited and educated from June 8 to 14, 2006 in Seoul, Korea. Two measurement tools were used: 'knowledge about the hereditary breast and ovarian cancer (HBOC)' and 'knowledge about the cancer genetics'. Results: Students' score of knowledge about HBOC at pre-education was $12.22{\pm}2.23$ and after education, it increased to $13.62{\pm}1.76$. This change was statistically significant (t=-3.253, p=.003). The score of knowledge about cancer genetics at pre-education was $11.31{\pm}3.44$, and after education it has increased to $16.17{\pm}1.94$. It also was statistically significant (t=-6.92, p=.000). Conclusion: This program was effective to be a starting point for establishing genetic educational planning for the oncology nurses in Korea. This academically-based course is recognized as valuable by oncology nurses. With this new knowledge, nurses can begin to expand their role in delivering comprehensive cancer care services in Korea.

• Genomics & Informatics
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• v.17 no.4
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• pp.47.1-47.12
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• 2019

The achievements of genome-wide association studies have suggested ways to predict diseases, such as type 2 diabetes (T2D), using single-nucleotide polymorphisms (SNPs). Most T2D risk prediction models have used SNPs in combination with demographic variables. However, it is difficult to evaluate the pure additive contribution of genetic variants to classically used demographic models. Since prediction models include some heritable traits, such as body mass index, the contribution of SNPs using unmatched case-control samples may be underestimated. In this article, we propose a method that uses propensity score matching to avoid underestimation by matching case and control samples, thereby determining the pure additive contribution of SNPs. To illustrate the proposed propensity score matching method, we used SNP data from the Korea Association Resources project and reported SNPs from the genome-wide association study catalog. We selected various SNP sets via stepwise logistic regression (SLR), least absolute shrinkage and selection operator (LASSO), and the elastic-net (EN) algorithm. Using these SNP sets, we made predictions using SLR, LASSO, and EN as logistic regression modeling techniques. The accuracy of the predictions was compared in terms of area under the receiver operating characteristic curve (AUC). The contribution of SNPs to T2D was evaluated by the difference in the AUC between models using only demographic variables and models that included the SNPs. The largest difference among our models showed that the AUC of the model using genetic variants with demographic variables could be 0.107 higher than that of the corresponding model using only demographic variables.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3879-3887
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• 2012

Background: Development of effective educational strategies should accompany increases in public awareness and the availability of genetic testing for breast cancer (BC). These educational strategies should be designed to fulfill the knowledge gap while considering factors that influence women's interest in order to facilitate decision making. Objective: To determine the possible correlates of Saudi women's interest in BC genes testing including socio-demographics, the level of awareness towards BC genes, the family history of BC and the perceived personal risk among adult Saudi women in Al Hassa, Saudi Arabia. Subjects and methods: This cross-sectional study was carried out during the second BC community-based campaign in Al Hassa, Saudi Arabia. All Saudi women aged ${\geq}18$ years (n=781) attending the educational components of the campaign were invited to a personal interview. Data collection included gathering information about sociodemographics, family history of BC, the perceived personal risk for BC, awareness and attitude towards BC genes and the women's interest in BC genes testing. Results: Of the included women (n=599), 19.5% perceived higher risk for BC development, significantly more among < 40 years of age, and with positive family history of BC before 50 years of age. The participants demonstrated a poor level of awareness regarding the inheritance, risk, and availability of BC genetic testing. The median summated knowledge score was 1.0 (out of 7 points) with a knowledge deficit of 87.8%. The level of knowledge showed significant decline with age (> 40 years). Of the included women 54.7% expressed an interest in BC genetic testing for assessing their BC risk. Multivariate regression model showed that being middle aged (Odds Ratio 'OR'=1.88, confidence intervals 'C.I'=1.14-3.11), with higher knowledge level (OR=1.67, C.I=1.08-2.57) and perceiving higher risk for BC (OR=2.11, C.I=1.61-2.76) were the significant positive correlates for Saudi women interest in BC genetic testing. Conclusion: Saudi women express high interest in genetic testing for BC risk despite their poor awareness. This great interest may reflect the presence of inappropriate information regarding BC genetic testing and its role in risk analysis.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7021-7027
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• 2014

Background: The problem of cancer, especially lung cancer, is very acute in Bangladesh. The present study was conducted to evaluate the risk of lung cancer among Bangladeshi people based on hereditary, socio-economic and demographic factors. Materials and Methods: This study was carried out in 208 people (patients-104, controls-104) from January 2012 to September 2013 using a structured questionnaire containing details of lung cancer risk factors including smoking, secondhand smoke, tobacco leaf intake, age, gender, family history, chronic lung diseases, radiotherapy in the chest area, diet, obesity, physical activity, alcohol consumption, occupation, education, and income. Descriptive statistics and testing of hypotheses were used for the analysis using SPSS software (version 20). Results: According to this study, lung cancer was more prevalent in males than females. Smoking was the highest risk factor (OR=9.707; RR=3.924; sensitivity=0.8872 and P<0.0001) followed by previous lung disease (asthma, tuberculosis etc.) (OR=7.095; RR=1.508; sensitivity=0.316 and P<0.0001)) for male patients. Highly cooked food (OR=2.485; RR=1.126; sensitivity=0.418 and P=0.004)) and also genetic inheritance (OR=1.93; RR=1.335; sensitivity=0.163 and P=0.138) demonstrated significant correlation with lung cancer as risk factors after these two and alcohol consumption was not prevalent. On the other hand, for female patients, tobacco leaf intake represented the highest risk (OR=2.00; RR=1.429; sensitivity= 0.667 and P=0.5603) while genetic inheritance and highly cooked food also correlate with lung cancer but not so significantly. Socioeconomic status and education level also play important roles in causing lung cancer. Some 78.5% male and 83.3% of female cancer patients were rural residents, while 58.2% lived at the margin or below the poverty line. Most male (39.8%) and female (50.0%) patients had completed only primary level education, and 27.6% male and 33.3% female patients were illiterate. Smoking was found to be more prevalent among the less educated persons. Conclusions: The results obtained in this study indicate the importance of creating awareness about lung cancer risk factors among Bangladeshi people and making appropriate access to health services for the illiterate, poor, rural people.

• Genomics & Informatics
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• v.10 no.3
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• pp.175-183
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• 2012

Colorectal cancer (CRC) is among the leading causes of cancer deaths and can be caused by environmental factors as well as genetic factors. Therefore, we developed a prediction model of CRC using genetic risk scores (GRS) and evaluated the effects of conventional risk factors, including family history of CRC, in combination with GRS on the risk of CRC in Koreans. This study included 187 cases (men, 133; women, 54) and 976 controls (men, 554; women, 422). GRS were calculated with most significantly associated single-nucleotide polymorphism with CRC through a genomewide association study. The area under the curve (AUC) increased by 0.5% to 5.2% when either counted or weighted GRS was added to a prediction model consisting of age alone (AUC 0.687 for men, 0.598 for women) or age and family history of CRC (AUC 0.692 for men, 0.603 for women) for both men and women. Furthermore, the risk of CRC significantly increased for individuals with a family history of CRC in the highest quartile of GRS when compared to subjects without a family history of CRC in the lowest quartile of GRS (counted GRS odds ratio [OR], 47.9; 95% confidence interval [CI], 4.9 to 471.8 for men; OR, 22.3; 95% CI, 1.4 to 344.2 for women) (weighted GRS OR, 35.9; 95% CI, 5.9 to 218.2 for men; OR, 18.1, 95% CI, 3.7 to 88.1 for women). Our findings suggest that in Koreans, especially in Korean men, GRS improve the prediction of CRC when considered in conjunction with age and family history of CRC.