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.
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.
People with higher genetic predisposition to obesity are more susceptible to cardiovascular diseases (CVDs) and healthy plant-based foods may be associated with reduced risks of obesity and other metabolic markers. We investigated whether healthy plant-foods-rich dietary patterns might have inverse associations with cardiometabolic risk factors in participants at genetically elevated risk of obesity. For this cross-sectional study, 377 obese and overweight women were chosen from health centers in Tehran, Iran. We calculated a healthy plant-based diet index (h-PDI) in which healthy plant foods received positive scores, and unhealthy plant and animal foods received reversed scores. A genetic risk score (GRS) was developed based on 3 polymorphisms. The interaction between GRS and h-PDI on cardiometabolic traits was analyzed using a generalized linear model (GLM). We found significant interactions between GRS and h-PDI on body mass index (BMI) (p = 0.02), body fat mass (p = 0.04), and waist circumference (p = 0.056). There were significant gene-diet interactions for healthful plant-derived diets and BMI-GRS on high-sensitivity C-reactive protein (p = 0.03), aspartate aminotransferase (p = 0.04), alanine transaminase (p = 0.05), insulin (p = 0.04), and plasminogen activator inhibitor 1 (p = 0.002). Adherence to h-PDI was more strongly related to decreased levels of the aforementioned markers among participants in the second or top tertile of GRS than those with low GRS. These results highlight that following a plant-based dietary pattern considering genetics appears to be a protective factor against the risks of cardiometabolic abnormalities.
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.
Lee, Jinyoung;Lee, Dongbin;Cho, Eun Young;Baek, Ji Hyun;Hong, Kyung Sue
Korean Journal of Schizophrenia Research
/
v.23
no.2
/
pp.65-70
/
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.
Shin, Sunghwan;Ryu, Mi Ra;Kwon, Won Kyung;Kim, Suhee;Jang, Ja-Hyun;Kim, Jong-Won
Journal of Genetic Medicine
/
v.18
no.1
/
pp.38-43
/
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.
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.
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.
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.
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.
본 웹사이트에 게시된 이메일 주소가 전자우편 수집 프로그램이나
그 밖의 기술적 장치를 이용하여 무단으로 수집되는 것을 거부하며,
이를 위반시 정보통신망법에 의해 형사 처벌됨을 유념하시기 바랍니다.
[게시일 2004년 10월 1일]
이용약관
제 1 장 총칙
제 1 조 (목적)
이 이용약관은 KoreaScience 홈페이지(이하 “당 사이트”)에서 제공하는 인터넷 서비스(이하 '서비스')의 가입조건 및 이용에 관한 제반 사항과 기타 필요한 사항을 구체적으로 규정함을 목적으로 합니다.
제 2 조 (용어의 정의)
① "이용자"라 함은 당 사이트에 접속하여 이 약관에 따라 당 사이트가 제공하는 서비스를 받는 회원 및 비회원을
말합니다.
② "회원"이라 함은 서비스를 이용하기 위하여 당 사이트에 개인정보를 제공하여 아이디(ID)와 비밀번호를 부여
받은 자를 말합니다.
③ "회원 아이디(ID)"라 함은 회원의 식별 및 서비스 이용을 위하여 자신이 선정한 문자 및 숫자의 조합을
말합니다.
④ "비밀번호(패스워드)"라 함은 회원이 자신의 비밀보호를 위하여 선정한 문자 및 숫자의 조합을 말합니다.
제 3 조 (이용약관의 효력 및 변경)
① 이 약관은 당 사이트에 게시하거나 기타의 방법으로 회원에게 공지함으로써 효력이 발생합니다.
② 당 사이트는 이 약관을 개정할 경우에 적용일자 및 개정사유를 명시하여 현행 약관과 함께 당 사이트의
초기화면에 그 적용일자 7일 이전부터 적용일자 전일까지 공지합니다. 다만, 회원에게 불리하게 약관내용을
변경하는 경우에는 최소한 30일 이상의 사전 유예기간을 두고 공지합니다. 이 경우 당 사이트는 개정 전
내용과 개정 후 내용을 명확하게 비교하여 이용자가 알기 쉽도록 표시합니다.
제 4 조(약관 외 준칙)
① 이 약관은 당 사이트가 제공하는 서비스에 관한 이용안내와 함께 적용됩니다.
② 이 약관에 명시되지 아니한 사항은 관계법령의 규정이 적용됩니다.
제 2 장 이용계약의 체결
제 5 조 (이용계약의 성립 등)
① 이용계약은 이용고객이 당 사이트가 정한 약관에 「동의합니다」를 선택하고, 당 사이트가 정한
온라인신청양식을 작성하여 서비스 이용을 신청한 후, 당 사이트가 이를 승낙함으로써 성립합니다.
② 제1항의 승낙은 당 사이트가 제공하는 과학기술정보검색, 맞춤정보, 서지정보 등 다른 서비스의 이용승낙을
포함합니다.
제 6 조 (회원가입)
서비스를 이용하고자 하는 고객은 당 사이트에서 정한 회원가입양식에 개인정보를 기재하여 가입을 하여야 합니다.
제 7 조 (개인정보의 보호 및 사용)
당 사이트는 관계법령이 정하는 바에 따라 회원 등록정보를 포함한 회원의 개인정보를 보호하기 위해 노력합니다. 회원 개인정보의 보호 및 사용에 대해서는 관련법령 및 당 사이트의 개인정보 보호정책이 적용됩니다.
제 8 조 (이용 신청의 승낙과 제한)
① 당 사이트는 제6조의 규정에 의한 이용신청고객에 대하여 서비스 이용을 승낙합니다.
② 당 사이트는 아래사항에 해당하는 경우에 대해서 승낙하지 아니 합니다.
- 이용계약 신청서의 내용을 허위로 기재한 경우
- 기타 규정한 제반사항을 위반하며 신청하는 경우
제 9 조 (회원 ID 부여 및 변경 등)
① 당 사이트는 이용고객에 대하여 약관에 정하는 바에 따라 자신이 선정한 회원 ID를 부여합니다.
② 회원 ID는 원칙적으로 변경이 불가하며 부득이한 사유로 인하여 변경 하고자 하는 경우에는 해당 ID를
해지하고 재가입해야 합니다.
③ 기타 회원 개인정보 관리 및 변경 등에 관한 사항은 서비스별 안내에 정하는 바에 의합니다.
제 3 장 계약 당사자의 의무
제 10 조 (KISTI의 의무)
① 당 사이트는 이용고객이 희망한 서비스 제공 개시일에 특별한 사정이 없는 한 서비스를 이용할 수 있도록
하여야 합니다.
② 당 사이트는 개인정보 보호를 위해 보안시스템을 구축하며 개인정보 보호정책을 공시하고 준수합니다.
③ 당 사이트는 회원으로부터 제기되는 의견이나 불만이 정당하다고 객관적으로 인정될 경우에는 적절한 절차를
거쳐 즉시 처리하여야 합니다. 다만, 즉시 처리가 곤란한 경우는 회원에게 그 사유와 처리일정을 통보하여야
합니다.
제 11 조 (회원의 의무)
① 이용자는 회원가입 신청 또는 회원정보 변경 시 실명으로 모든 사항을 사실에 근거하여 작성하여야 하며,
허위 또는 타인의 정보를 등록할 경우 일체의 권리를 주장할 수 없습니다.
② 당 사이트가 관계법령 및 개인정보 보호정책에 의거하여 그 책임을 지는 경우를 제외하고 회원에게 부여된
ID의 비밀번호 관리소홀, 부정사용에 의하여 발생하는 모든 결과에 대한 책임은 회원에게 있습니다.
③ 회원은 당 사이트 및 제 3자의 지적 재산권을 침해해서는 안 됩니다.
제 4 장 서비스의 이용
제 12 조 (서비스 이용 시간)
① 서비스 이용은 당 사이트의 업무상 또는 기술상 특별한 지장이 없는 한 연중무휴, 1일 24시간 운영을
원칙으로 합니다. 단, 당 사이트는 시스템 정기점검, 증설 및 교체를 위해 당 사이트가 정한 날이나 시간에
서비스를 일시 중단할 수 있으며, 예정되어 있는 작업으로 인한 서비스 일시중단은 당 사이트 홈페이지를
통해 사전에 공지합니다.
② 당 사이트는 서비스를 특정범위로 분할하여 각 범위별로 이용가능시간을 별도로 지정할 수 있습니다. 다만
이 경우 그 내용을 공지합니다.
제 13 조 (홈페이지 저작권)
① NDSL에서 제공하는 모든 저작물의 저작권은 원저작자에게 있으며, KISTI는 복제/배포/전송권을 확보하고
있습니다.
② NDSL에서 제공하는 콘텐츠를 상업적 및 기타 영리목적으로 복제/배포/전송할 경우 사전에 KISTI의 허락을
받아야 합니다.
③ NDSL에서 제공하는 콘텐츠를 보도, 비평, 교육, 연구 등을 위하여 정당한 범위 안에서 공정한 관행에
합치되게 인용할 수 있습니다.
④ NDSL에서 제공하는 콘텐츠를 무단 복제, 전송, 배포 기타 저작권법에 위반되는 방법으로 이용할 경우
저작권법 제136조에 따라 5년 이하의 징역 또는 5천만 원 이하의 벌금에 처해질 수 있습니다.
제 14 조 (유료서비스)
① 당 사이트 및 협력기관이 정한 유료서비스(원문복사 등)는 별도로 정해진 바에 따르며, 변경사항은 시행 전에
당 사이트 홈페이지를 통하여 회원에게 공지합니다.
② 유료서비스를 이용하려는 회원은 정해진 요금체계에 따라 요금을 납부해야 합니다.
제 5 장 계약 해지 및 이용 제한
제 15 조 (계약 해지)
회원이 이용계약을 해지하고자 하는 때에는 [가입해지] 메뉴를 이용해 직접 해지해야 합니다.
제 16 조 (서비스 이용제한)
① 당 사이트는 회원이 서비스 이용내용에 있어서 본 약관 제 11조 내용을 위반하거나, 다음 각 호에 해당하는
경우 서비스 이용을 제한할 수 있습니다.
- 2년 이상 서비스를 이용한 적이 없는 경우
- 기타 정상적인 서비스 운영에 방해가 될 경우
② 상기 이용제한 규정에 따라 서비스를 이용하는 회원에게 서비스 이용에 대하여 별도 공지 없이 서비스 이용의
일시정지, 이용계약 해지 할 수 있습니다.
제 17 조 (전자우편주소 수집 금지)
회원은 전자우편주소 추출기 등을 이용하여 전자우편주소를 수집 또는 제3자에게 제공할 수 없습니다.
제 6 장 손해배상 및 기타사항
제 18 조 (손해배상)
당 사이트는 무료로 제공되는 서비스와 관련하여 회원에게 어떠한 손해가 발생하더라도 당 사이트가 고의 또는 과실로 인한 손해발생을 제외하고는 이에 대하여 책임을 부담하지 아니합니다.
제 19 조 (관할 법원)
서비스 이용으로 발생한 분쟁에 대해 소송이 제기되는 경우 민사 소송법상의 관할 법원에 제기합니다.
[부 칙]
1. (시행일) 이 약관은 2016년 9월 5일부터 적용되며, 종전 약관은 본 약관으로 대체되며, 개정된 약관의 적용일 이전 가입자도 개정된 약관의 적용을 받습니다.