Focusing on complex diseases of public health significance, strategic issues regarding the on-going Korean Genome Cohort were reviewed: target size and diseases, measurements, study design issues, and followup strategy of the cohort. Considering the epidemiologic characteristics of Korean population as well as strengths and drawbacks of current research environment, we tried to tailor the experience of other existing cohorts into proposals for this Korean study. Currently 100,000 individuals have been participating the new Genome Cohort in Korea. Target size of de novo collection is recommended to be set as between 300,000 to 500,000. This target size would allow acceptable power to detect genetic and environmental factors of moderate effect size and possible interactions between them. Family units and/or special subgroups are recommended to parallel main body of adult individuals to increase the overall efficiency of the study. Given that response rate to the conventional re-contact method may not be satisfactory, successful follow-up is the main key to the achievement of the Korean Genome Cohort. Access to the central database such as National Health Insurance data can provide enormous potential for near-complete case detection. Efforts to build consensus amongst scientists from broad fields and stakeholders are crucial to unleash the centralized database as well as to refine the commitment of this national project.
Human Genome Project (HGP) could unveil the secrets of human being by a long script of genetic codes, which enabled us to get access to mine the cause of diseases more efficiently. Two wheels for HGP, bioinformatics and high throughput technology are essential techniques for the genomic medicine. While microarray platforms are still evolving, we can screen more than 500,000 genotypes at once. Even we can sequence the whole genome of an organism within a day. Because the future medicne will focus on the genetic susceptibility of individuals, we need to find genetic variations of each person by efficient genotyping methods.
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When conducting large-scale cohort studies, numerous statistical issues arise from the range of study design, data collection, data analysis and interpretation. In genomic cohort studies, these statistical problems become more complicated, which need to be carefully dealt with. Rapid technical advances in genomic studies produce enormous amount of data to be analyzed and traditional statistical methods are no longer sufficient to handle these data. In this paper, we reviewed several important statistical issues that occur frequently in large-scale genomic cohort studies, including measurement error and its relevant correction methods, cost-efficient design strategy for main cohort and validation studies, inflated Type I error, gene-gene and gene-environment interaction and time-varying hazard ratios. It is very important to employ appropriate statistical methods in order to make the best use of valuable cohort data and produce valid and reliable study results.
Power and sample size estimation is one of the crucially important steps in planning a genetic association study to achieve the ultimate goal, identifying candidate genes for disease susceptibility, by designing the study in such a way as to maximize the success possibility and minimize the cost. Here we review the optimal two-stage genotyping designs for genomewide association studies recently investigated by Wang et al(2006). We review two mathematical frameworks most commonly used to compute power in genetic association studies prior to the main study: Monte-Carlo and non-central chi-square estimates. Statistical powers are computed by these two approaches for case-control genotypic tests under one-stage direct association study design. Then we discuss how the linkagedisequilibrium strength affects power and sample size, and how to use empirically-derived distributions of important parameters for power calculations. We provide useful information on publicly available softwares developed to compute power and sample size for various study designs.
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During the last decade, genomic cohort study has been developed in many countries by linking health data and genetic data in stored samples. Genomic cohort study is expected to find key genetic components that contribute to common diseases, thereby promising great advance in genome medicine. While many countries endeavor to build biobank systems, biobank-based genome research has raised important ethical concerns including genetic privacy, confidentiality, discrimination, and informed consent. Informed consent for biobank poses an important question: whether true informed consent is possible in populationbased genomic cohort research where the nature of future studies is unforeseeable when consent is obtained. Due to the sensitive character of genetic information, protecting privacy and keeping confidentiality become important topics. To minimize ethical problems and achieve scientific goals to its maximum degree, each country strives to build population-based genomic cohort research project, by organizing public consultation, trying public and expert consensus in research, and providing safeguards to protect privacy and confidentiality.
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OBJECTIVES Recent educational efforts have concentrated on patient's early hospital arrival after symptom onset. The purpose of this study was to evaluate the time interval between symptom onset and hospital arrival and to investigate its relation with clinical outcomes for patients with acute ischemic stroke. METHODS: A prospective registry of patients with signs or symptoms of acute ischemic stroke, admitted to the OO Medical Center through emergency room, was established from September 2003 to December 2004. The interval betwee symptom onset and hospital arrival was recorded for each eligible patient and analyzed together with clinical characteristics, medication type, severity of neurologic deficits, and functional outcomes. RESULTS: Based on the data of 256 patients, the median interval between symptom onset and hospital arrival was 13 hours, and 22% of patients were admitted to the hospital within 3 hours after symptom onset. Patients of not-mild initial severity and functional status showed significant differences between arrival hours of 0-3 and later than 3 in terms of their functional outcomes on discharge. Logistic regression models also showed that arrival within 3 hours was a significant factor influencing functional outcome (OR=5.6; 95% CI=2.1, 15.0), in addition to patient's initial severity, old age, cardioembolism subtype, and referral to another hospital. CONCLUSIONS: The time interval between symptom onset and hospital arrival significantly influenced treatment outcome for patients with acute ischemic stroke, even after controlling for other significant clinical characteristics. The findings provided initiatives for early hospital arrival of patients and improvement of emergency medical system.
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OBJECTIVES According to Rowe and Kahn (1998), successful aging is the combination of a low probability of disease, high functioning, and active engagement with life. The purpose of this study was to assess the relationship between active engagement with life and functioning among the community-dwelling elderly. METHODS: Data were collected from Wave 2 of the Suwon Longitudinal Aging Study (SLAS), consisting of a sample of 645 persons aged 65 and older living in the community. A social activity checklist and social support inventory were used as measures of engagement with life, along with the Physical Functioning (PF) scale as a measure of functioning. The effects of social support and social activity on physical functioning, taking into account the covariates, were analyzed by hierarchical linear regression analysis. RESULTS: Maintenance of social activity and social support were significantly associated with higher physical function, after adjusting for sociodemographic and healthrelated covariates. Social support appeared to be more prominent than social activity in predicting physical functioning. CONCLUSIONS: Social support and social activity are potentially modifiable factors associated with physical function in older persons. Studies examining the role social engagement may play in preventing disability are warranted.
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OBJECTIVES This study characterized the extent to which youth depressive symptoms, parental alcohol problems, and parental drinking account for differences in alcoholrelated problems among a large sample of adolescent females. METHODS: The stratified sample consists of 2077 adolescent females from twelve female-only high schools located in a large metropolitan city in the Republic of Korea. Students completed a questionnaire about alcohol use nd alcohol problems, their parents' alcohol problems, and a number of risk and protective factors. Data were analyzed using tobit regression analyses to better characterize the associations among variables. RESULTS: Almost two-thirds of students who consume alcohol had experienced at least one to two alcohol-related problems in their lives and 54.6% reported at least one current symptom of depression, with nearly one-third reporting two depressive symptoms. Two-thirds of the students indicated that at least one parent had an alcoholrelated problem, and that approximately 29% had experie nced several problems. Results of tobit regression analyses indicate that youth alcohol-related problems are positively associated with depressive symptoms (p<0.01) and parent drinking problems (p<0.05). Parental drinking is no longer significant when the variable parental attention is added to the model. Decomposition of the tobit parameters shows that for every unit of increase in depressive symptoms and in parent drinking problems, the probability of a youth experiencing alcohol problems increases by 6% and 1%, respectively. For every unit of increase in parental attention, the probability of youth experiencing drinking problems decreases by 5%. CONCLUSIONS: This study presents evidence that alcoholrelated problems and depressive symptoms are highly prevalent among adolescent females. Although a comprehensive public health approach is needed to address drinking and mental health problems, different interventions are needed to target factors associated with initiation of alcohol problems and those associated with increased alcohol problems among those who already began experiencing such problems.
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OBJECTIVES The aim of this study is to identify factors determining the purchase of private health insurance under the mandatory National Health Insurance(NHI) system in Korea. METHODS: The data were collected by the National Cancer Center in Korea. It includes cancer patients who were newly diagnosed with stomach (ICD code, C16), lung(C33-C34), liver (C22), colorectal cancer(C18-C20) or breast(C50) cancer. Data were gathered from the hospital Order Communication System (OCS), medical records, and face-to-face interviews, using a structured questionnaire. Clinical, socio-demographic and private health insurance related factors were also gathered. RESULTS: Overall, 43.9% of patients had purchased one or more private health insurance schemes related to cancer, with an average monthly premium of won 65,311 and an average benefit amount of won 19 million. Females, younger aged, high income earners, national health insurers and metropolitan citizens were more likely to purchase private health insurance than their counterparts. CONCLUSIONS: About half of Korean people have supplementary private health insurance and their benefits are sufficient to cover the out-of-pocket fees required for cancer treatment, but inequality remains in the purchase of private health insurance. Further studies are needed to investigate the impacts of private health insurance on NHI, and the relationship between cancer patients' burden and benefits.
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OBJECTIVES Bisphenol A diglycidyl ether (BADGE) is the major component in commercial liquid epoxy resins, which are manufactured by co-reacting bisphenol A with epichlorohydrin. This study was performed to show the developmental effects of prenatal and postnatal exposures to BADGE in male rat offspring. METHODS: Mated female rats were divided into four groups, each containing 12 rats. The dosing solutions were prepared by thoroughly mixing BADGE in corn oil at the 0, 375, 1500 and 3000 mg/kg/day concentrations. Mated females were dosed once daily by oral gavage on gestation day (GD) 6 - 20 and postnatal day (PND) 0 - 21. Pregnant female dams were observed general symptoms and body weight. Also, male pups were observed the general symptoms, body weight, developmental parameters (e.g. anogenital distance, pina detachment, incisor eruption, nipple retention, eye opening, testis descent), organ pathologic changes and hormone levels of plasma. RESULTS: Pregnant rats treated with BADGE died at a rate of about 70% in the 1500 mg/kg/day group and all rats treated with 3000 mg/kg/day died. Body weight, for male pups treated with doses of 375 mg/kg/day, was significantly lower than in the control group at PND 42, 56, and 63 (p<0.05). Evaluation of body characteristics including; separation of auricle, eruption of incisor, separation of eyelid, nipple retention, descent of testis, and separation of the prepuce in the BADGE treated group showed no difference in comparisons with the control group. AGD and adjusted AGD (mm/kg) for general developmental items in BADGE 375 mg/kg/day treated pups tended to be longer than in controls, however, these differences were not statistically significant. Relative weights of adrenal gland, lung (p<0.05), brain, epididymis, prostate, and testis (p<0.01) were heavier than in control in measures at PND 9 weeks. There were no significant changes in comparisons of histological findings of these organs. Loss of spermatids was observed in the seminiferous tubule at PND 9 weeks, but no weight changes were observed. The plasma estrogen levels were similar in the control and treatment groups at PND 3, 6 and 9 weeks. The plasma testosterone levels in the control group tended to increase with age. However, in the BADGE 375 mg/kg/day treated male pups it did not tend to increase. CONCLUSIONS: These findings suggest that BADGE is a chemical that has developmental effects consistent with it being an endocrine disruptor.
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OBJECTIVES This prospective population-based cohort study was conducted to evaluate the risk factors of cognitive impairment and the degree of cognitive function change through a 5-year follow-up. METHODS: The baseline and follow-up surveys were conducted in 1998 and 2003, respectively. Among 176 subjects who had normal cognitive function in the baseline study, 136 were followed up for 5 years. The cognitive function was investigated using the Korean version of the Mini-Mental State Examination (MMSE-K). The collected data were analyzed using SPSS and Stata. RESULTS: Of the 136 subjects analyzed, 25 (18.4%) were cognitively impaired. Old age and low social support in the baseline survey were risk factors for cognitive impairment after 5 years. In the generalized estimating equation for 128 subjects except severe cognitive impairment about the contributing factors of cognitive function change, the interval of 5 years decreased MMSE-K score by 1.02 and the cognitive function was adversely affected with increasing age, decreasing education and decreasing social support. CONCLUSIONS: Although the study population was small, it was considered that the study results can be used to develop a community-based prevention system for cognitive impairment.
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OBJECTIVES This study was conducted to elicit quality weights for 42 EQ-5D health states with the time trade-off (TTO) method from the general population of South Korea. METHODS: We selected the same EQ-5D health states as those in the UK MVH study. The Korean version of EQ-5D questionnaire and TTO method were used for the valuation process. We interviewed 500 people as a representative sample of the general population in Seoul and Gyeonggido. The result was compared with those from UK, Japan, and USA by Spearman's rank correlation and t-test. RESULTS: TTO values for 42 EQ-5D health states and 'unconscious' state were obtained from the general South Korean population. The best one was '11112' state and the worst one was 'unconscious' state. The states worse than death were '33323', '33333', and 'unconscious' states, which had negative TTO values. There was a strong correlation between TTO values of the EQ-5D health states and those of their corresponding states from UK, Japan, and USA (Spearman's correlation coefficient: 0.885, 0.882, and 0.944, respectively, p <0.001). However, absolute TTO values of most EQ-5D health states were significantly different from those of their corresponding states in other foreign studies (UK: 41/42, USA: 32/42, Japan: 15/17). CONCLUSIONS: We found that the Korean general population TTO values for EQ-5D health states were different from those of other foreign studies, suggesting that a specific Korean valuation set should be developed and used for economic evaluation studies in South Korea.
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OBJECTIVES Since the first human infection from avian influenza was reported in Hong Kong in 1997, many Asian countries have confirmed outbreaks of highly pathogenic H5N1 avian influenza viruses. In addition to Asian countries, the EU authorities also held an urgent meeting in February 2006 at which it was agreed that Europe could also become the next target for H5N1 avian influenza in the near future. In this paper, we provide the general and applicable information on the avian influenza in the bioinformatics field to assist future studies in preventive medicine. METHODS: We introduced some up-to-date analytical tools in bioinformatics research, and discussed the current trends of avian influenza outbreaks. Among the bioinformatics methods, we focused our interests on two topics: attern analysis using the secondary database of avian influenza, and structural analysis using the molecular dynamics simulations in vaccine design. RESULTS: Use of the public genome databases available in the bioinformatics field enabled intensive analysis of the genetic patterns. Moreover, molecular dynamic simulations have also undergone remarkable development on the basis of the high performance supercomputing infrastructure these days. CONCLUSIONS: The bioinformatics techniques we introduced in this study may be useful in preventive medicine, especially in vaccine and drug discovery.
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