The final decision of study design in molecular and genetic epidemiology is usually a compromise between the research study aims and a number of logistical and ethical barriers that may limit the feasibility of the study or the interpretation of results. Although biomarker measurements may improve exposure or disease assessments, it is necessary to address the possibility that biomarker measurement inserts additional sources of misclassification and confounding that may lead to inconsistencies across the research literature. Studies targeting multi-causal diseases and investigating gene-environment interactions must not only meet the needs of a traditional epidemiologic study but also the needs of the biomarker investigation. This paper is intended to highlight the major issues that need to be considered when developing an epidemiologic study utilizing biomarkers. These issues covers from molecular and genetic epidemiology (MGE) study designs including cross-sectional, cohort, case-control, clinical trials, nested case-control, and case-only studies to matching the study design to the MGE research goals. This review summarizes logistical barriers and the most common epidemiological study designs most relevant to MGE and describes the strengths and limitations of each approach in the context of common MGE research aims to meet specific MEG objectives.
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The Search for Clinically Useful Biomarkers of Complex Disease: A Data Analysis Perspective Elizabeth C. Considine Metabolites.2019; 9(7): 126. CrossRef
Levels and predictors of airborne and internal exposure to manganese and iron among welders Beate Pesch, Tobias Weiss, Benjamin Kendzia, Jana Henry, Martin Lehnert, Anne Lotz, Evelyn Heinze, Heiko Udo Käfferlein, Rainer Van Gelder, Markus Berges, Jens-Uwe Hahn, Markus Mattenklott, Ewald Punkenburg, Andrea Hartwig, Thomas Brüning Journal of Exposure Science & Environmental Epidemiology.2012; 22(3): 291. CrossRef
Biomarkers are characteristic biological properties that can be detected and measured in a variety of biological matrices in the human body, including the blood and tissue, to give an indication of whether there is a threat of disease, if a disease already exists, or how such a disease may develop in an individual case. Along the continuum from exposure to clinical disease and progression, exposure, internal dose, biologically effective dose, early biological effect, altered structure and/or function, clinical disease, and disease progression can potentially be observed and quantified using biomarkers. While the traditional discovery of biomarkers has been a slow process, the advent of molecular and genomic medicine has resulted in explosive growth in the discovery of new biomarkers. In this review, issues in evaluating biomarkers will be discussed and the biomarkers of environmental exposure, early biologic effect, and susceptibility identified and validated in epidemiological studies will be summarized. The spectrum of genomic approaches currently used to identify and apply biomarkers and strategies to validate genomic biomarkers will also be discussed.
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Could 8-oxoguanine DNA glycosylase 1 Ser326Cys polymorphism be a biomarker of susceptibility in cancer? Bensu Karahalil, Ayşe Başak Engin, Erdem Coşkun Toxicology and Industrial Health.2014; 30(9): 814. CrossRef
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In the more than 100 genome wide association studies (GWAS) conducted in the past 5 years, more than 250 genetic loci contributing to more than 40 common diseases and traits have been identified. Whilst many genes have been linked to a trait, both their individual and combined effects are small and unable to explain earlier estimates of heritability. Given the rapid changes in disease incidence that cannot be accounted for by changes in diagnostic practises, there is need to have well characterized exposure information in addition to genomic data for the study of gene-environment interactions. The case-control and cohort study designs are most suited for studying associations between risk factors and occurrence of an outcome. However, the case control study design is subject to several biases and hence the preferred choice of the prospective cohort study design in investigating gene-environment interactions. A major limitation of utilising the prospective cohort study design is the long duration of follow-up of participants to accumulate adequate outcome data. The GWAS paradigm is a timely reminder for traditional epidemiologists who often perform one- or few-at-a-time hypothesis-testing studies with the main hallmarks of GWAS being the agnostic approach and the massive dataset derived through large-scale international collaborations.
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Genetic factors clearly play a role in carcinogenesis, but migrant studies provide unequivocal evidence that environmental factors are critical in defining cancer risk. Therefore, one may expect that the lower availability of substrate for biochemical reactions leads to more genetic changes in enzyme function; for example, most studies have indicated the variant MTHFR genotype 677TT is related to biomarkers, such as homocysteine concentrations or global DNA methylation particularly in a low folate diet. The modification of a phenotype related to a genotype, particularly by dietary habits, could support the notion that some of inconsistencies in findings from molecular epidemiologic studies could be due to differences in the populations studied and unaccounted underlying characteristics mediating the relationship between genetic polymorphisms and the actual phenotypes. Given the evidence that diet can modify cancer risk, gene-diet interactions in cancer etiology would be anticipated. However, much of the evidence in this area comes from observational epidemiology, which limits the causal inference. Thus, the investigation of these interactions is essential to gain a full understanding of the impact of genetic variation on health outcomes. This report reviews current approaches to gene-diet interactions in epidemiological studies. Characteristics of gene and dietary factors are divided into four categories: one carbon metabolism-related gene polymorphisms and dietary factors including folate, vitamin B group and methionines; oxidative stress-related gene polymorphisms and antioxidant nutrients including vegetable and fruit intake; carcinogen-metabolizing gene polymorphisms and meat intake including heterocyclic amins and polycyclic aromatic hydrocarbon; and other gene-diet interactive effect on cancer.
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Genetic Variants in Folate and Cobalamin Metabolism-Related Genes in Pregnant Women of a Homogeneous Spanish Population: The Need for Revisiting the Current Vitamin Supplementation Strategies Gemma Rodriguez-Carnero, Paula M. Lorenzo, Ana Canton-Blanco, Leire Mendizabal, Maddi Arregi, Mirella Zulueta, Laureano Simon, Manuel Macia-Cortiñas, Felipe F. Casanueva, Ana B. Crujeiras Nutrients.2022; 14(13): 2702. CrossRef
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Genetic polymorphisms and folate status Mami Hiraoka, Yasuo Kagawa Congenital Anomalies.2017; 57(5): 142. CrossRef
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Comprehensive Evaluation of One-Carbon Metabolism Pathway Gene Variants and Renal Cell Cancer Risk Todd M. Gibson, Paul Brennan, Summer Han, Sara Karami, David Zaridze, Vladimir Janout, Helen Kollarova, Vladimir Bencko, Marie Navratilova, Neonila Szeszenia-Dabrowska, Dana Mates, Alena Slamova, Ruth M. Pfeiffer, Rachael Z. Stolzenberg-Solomon, Susan T. PLoS ONE.2011; 6(10): e26165. CrossRef
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In this article, we reviewed the literature on risk assessment (RA) models with and without molecular genomic markers and the current utility of the markers in the pharmacogenetic field. Epidemiological risk assessment is applied using statistical models and equations established from current scientific knowledge of risk and disease. Several papers have reported that traditional RA tools have significant limitations in decision-making in management strategies for individuals as predictions of diseases and disease progression are inaccurate. Recently, the model added information on the genetic susceptibility factors that are expected to be most responsible for differences in individual risk. On the continuum of health care, from diagnosis to treatment, pharmacogenetics has been developed based on the accumulated knowledge of human genomic variation involving drug distribution and metabolism and the target of action, which has the potential to facilitate personalized medicine that can avoid therapeutic failure and serious side effects. There are many challenges for the applicability of genomic information in a clinical setting. Current uses of genetic markers for managing drug therapy and issues in the development of a valid biomarker in pharmacogenetics are discussed.
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Effect of genetic and environmental influences on cardiometabolic risk factors: a twin study György Jermendy, Tamás Horváth, Levente Littvay, Rita Steinbach, Ádám L Jermendy, Ádám D Tárnoki, Dávid L Tárnoki, Júlia Métneki, János Osztovits Cardiovascular Diabetology.2011; 10(1): 96. CrossRef
OBJECTIVES This study was performed to evaluate the effectiveness of 'village health worker training program' which aimed to build community participatory health promotion capacity of community leaders in villages of low developed country and to develop methods for further development of the program. METHODS: The intervention group were 134 community leaders from 25 barangays (village). Control group were 149 form 4 barangays. Intervention group participated 3-day training program. Questionnaire was developed based on 'Health Promotion Capacity Checklist' which assessed capacity in 4 feathers; 'knowledge', 'skill', 'commitment', and 'resource'. Each feather was assessed in 4 point rating scale. Capacity scores between intervention group and control group were examined to identify changes between the pre- and post-intervention periods. A qualitative evaluation of the program was conducted to assess the appropriateness of the program. The program was conducted in Tuguegarao city, Philippine in January, 2009. RESULTS: The result showed significant increases in the total health promotion capacity and each feather of health promotion capacities between pre and post assessment of intervention group. But there was no significant change in that of control group. Participants marked high level of satisfaction for preparedness, selection of main subjects and education method. Qualitative evaluation revealed that training program facilitated community participatory health promotion capacity of participants. CONCLUSIONS: This study suggested that the Village health worker training program is effective for building health promotion capacity of community leaders and it can be a main method for helping low developed countries with further development.
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Evaluation of global health capacity building initiatives in low-and middle-income countries: A systematic review Hady Naal, Maria El Koussa, Melissa El Hamouch, Layal Hneiny, Shadi Saleh Journal of Global Health.2020;[Epub] CrossRef
Unintended Benefits: Leadership Skills and Behavioral Change among Guatemalan Fieldworkers Employed in a Longitudinal Household Air Pollution Study Devina Kuo, Lisa M. Thompson, Amy Lee, Carolina Romero, Kirk R. Smith International Quarterly of Community Health Education.2011; 31(4): 311. CrossRef
Ji Yeon Shin, Jun Hyun Hwang, Jin Young Jeong, Sung Hi Kim, Jai Dong Moon, Sang Chul Roh, Young Wook Kim, Yangho Kim, Jong Han Leem, Young Su Ju, Young Seoub Hong, Eun Hee Ha, Yong Hwan Lee, Duk Hee Lee, Dong Hyun Kim
OBJECTIVES This cross-sectional study was performed to examine if the serum gamma-glutamyltransferase (GGT) level that is within its normal range is associated with the risk of type 2 diabetes and if the association between the waist hip ratio (WHR) and type 2 diabetes is different depending on the serum GGT levels. METHODS: The study subjects were 23,436 persons aged 40 years or older and who participated in regular health check-ups at 11 hospitals (males: 5,821, females: 17,615). The gender-specific quintiles of the serum GGT and WHR were used to examine the associations with type 2 diabetes. RESULTS: The serum GGT levels within their normal range were positively associated with type 2 diabetes only in women. The adjusted odds ratios (ORs) were 1.0, 1.0, 1.4, 2.1, and 2.5 according to the quintiles of the serum GGT (p(trend)<0.01). The WHR was more strongly associated with the prevalence of diabetes among the women with a high-normal serum GGT level as compared with those with a low-normal serum GGT level (p for interaction=0.02). For example, the adjusted ORs for women with a low normal serum GGT level were 1.0, 1.2, 1.5, 2.2, and 2.4 according to the quintiles of the WHR, while those figures were 1.0, 2.4, 3.6, 5.0, and 8.3 among the women with a high normal serum GGT level. However, in men, the serum GGT was very weakly associated with type 2 diabetes and the association between the WHR and type 2 diabetes was not different depending on the serum GGT level. CONCLUSIONS: Serum GGT within its normal range was positively associated with type 2 diabetes, and central obesity was more strongly associated with the prevalence of type 2 diabetes when the serum GGT level was high-normal. However, these associations were observed only in women, which is different from the previous findings. The stronger relation between central obesity and type 2 diabetes among women with a high-normal serum GGT level can be useful for selecting a group that is at high risk for type 2 diabetes irregardless of whatever the underlying mechanism is.
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Serum gamma-glutamyl transferase and risk of type 2 diabetes in the general Korean population: a Mendelian randomization study Youn Sue Lee, Yoonsu Cho, Stephen Burgess, George Davey Smith, Caroline L. Relton, So-Youn Shin, Min-Jeong Shin Human Molecular Genetics.2016; 25(17): 3877. CrossRef
Different associations between obesity and impaired fasting glucose depending on serum gamma-glutamyltransferase levels within normal range: a cross-sectional study Nam Soo Hong, Jeong-Gook Kim, Yu-Mi Lee, Hyun-Woo Kim, Sin Kam, Keon-Yeop Kim, Ki-Su Kim, Duk-Hee Lee BMC Endocrine Disorders.2014;[Epub] CrossRef
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OBJECTIVES The aims of this paper were to develop the composite deprivation index (CDI) for the sub-district (Eup-Myen-Dong) levels based on the theory of social exclusion and to explore the relationship between the CDI and the standardized mortality ratio (SMR). METHODS: The paper calculated the age adjusted SMR and we included five dimensions of social exclusion for CDI; unemployment, poverty, housing, labor and social network. The proxy variables of the five dimensions were the proportion of unemployed males, the percent of recipients receiving National Basic Livelihood Security Act benefits, the proportion of households under the minimum housing standard, the proportion of people with a low social class and the proportion of single-parent household. All the variables were standardized using geometric transformation and then we summed up them for a single index. The paper utilized the 2004-2006 National Death Registry data, the 2003-2006 national residents' registration data, the 2005 Population Census data and the 2005-2006 means-tested benefit recipients' data. RESULTS: The figures were 115.6, 105.8 and 105.1 for the CDI of metropolitan areas (big cities), middle size cities and rural areas, respectively. The distributional variation of the CDI was the highest in metropolitan areas (8.9 - 353.7) and the lowest was in the rural areas (26.8 - 209.7). The extent and relative differences of deprivation increased with urbanization. Compared to the Townsend and Carstairs index, the CDI better represented the characteristics of rural deprivation. The correlation with the SMR was statistically significant and the direction of the CDI effects on the SMR was in accordance with that of the previous studies. CONCLUSIONS: The study findings indicated mortality inequalities due to the difference in the CDI. Despite the attempt to improve deprivation measures, further research is warranted for the consensus development of a deprivation index.
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Development of an Index for Diagnosing Regional Inequality Levels and Analysis of Characteristics by Region So-Yeong Lee, Jun-Yub Choi, Hee-Sun Joo Journal of Korea Planning Association.2024; 59(4): 5. CrossRef
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The association between greenness exposure and COVID-19 incidence in South Korea: An ecological study Kyung-Shin Lee, Hye Sook Min, Jae-Hyun Jeon, Yoon-Jung Choi, Ji Hwan Bang, Ho Kyung Sung Science of The Total Environment.2022; 832: 154981. CrossRef
The cost- effectiveness of early dental visit in infants and toddlers focused on regional deprivation in South Korea: A retrospective cohort study Eunsuk Ahn, Sun-Mi Kim, Charu C. Garg PLOS ONE.2022; 17(6): e0269770. CrossRef
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Do persons with low socioeconomic status have less access to greenspace? Application of accessibility index to urban parks in Seoul, South Korea Seulkee Heo, Amruta Nori-Sarma, Sera Kim, Jong-Tae Lee, Michelle L Bell Environmental Research Letters.2021; 16(8): 084027. CrossRef
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OBJECTIVES The amount of medical utilization by Medical Aid recipients was 3.7 times that of patients with Korean Medical Insurance. This study aims to describe the surplus medicine and the medication-related utilization, and to determine factors contributing to surplus medicine. METHODS: Among those who used copayment-free Class I Medical Aid in 2005, 146,880 subjects who were > or =19 year-old and received >365 days medical treatment per year were studied with their case managers by conducting face-to-face interviews. The analytic methods were description, chi-square, t-tests, ANCOVA and multiple logistic regressions. RESULTS: Most subjects were female (68.6%), the elderly (62.5%), and the separated (61.6%), had an elementary graduation or less (74.8%), and had disabilities (33.2%). The percentage of subjects with surplus medicine was 18.5%. However, the percentage of females, the elderly, those with non-disabilities, the separated, the uneducated, those with a very poor perceived health status and those with an economical burden for medical treatment was 19.3%, 18.9%, 19.0%, 19.3%, 19.0%, 20.2% and 24.3%, respectively. For subjects with surplus medicine, averages for the number of used pharmacies, the pharmacy-visit days and the medication costs were 4.6 drugstores, 34.9 days and approximately 1,124 thousand Won. These values were higher than those without surplus medicine (4.4 drugstores , 33.8 days, and 1,110 thousand won, respectively). The odds ratios of the contributing factors to surplus medicine were female 1.11 (95% CI=1.07-1.14), the elderly 1.06 (95% CI=1.02-1.10), those with non-disabilities 1.08 (95% CI=1.05-1.12), the separated 1.14 (95% CI=1.10-1.18), the unmarried 1.12 (95% CI=1.07-1.18), the uneducated 1.03 (95% CI=1.01-1.08), those with a very poor perceived health status 1.04 (95% CI=1.01-1.08) and experiencing an economical burden for medical treatment 2.33 (95% CI=2.26-2.40). CONCLUSIONS: 18.5% of subjects had surplus medicine with a higher mean of medication cost. Therefore, health education and health promotion programs to prevent surplus medicine and to improve the appropriate usage of medication are necessary.
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OBJECTIVES This study was performed to investigate the mumps transmission control status and inapparent infection rate among middle and high school students in Daegu City during a mumps outbreak. METHODS: Nine schools (two middle schools and seven high schools), which reported a number of mumps cases between 2007 and 2008 were selected for investigation. During March-May 2008, a standard questionnaire was distributed to gather information about case identification, instructed isolation measure, isolation status of mumps cases and related factors, and outdoor activities of non-isolated mumps case. Inapparent infection rate was estimated by serum mumps IgM and IgG antibodies status and self-reported mumps symptoms in three of the nine schools. RESULTS: Among 2,560 respondents, more than half of students answered that they did not receive instructions in mumps transmission control measures during the outbreak. Among the 327 mumps cases identified by the questionnaire, 131 cases (40.1%) were considered as isolated and the isolation rates were significantly different among schools, grades, and gender. Of the non-isolated cases, 88.3% continued attending school. Inapparent mumps infection rates were between 56.3% and 70.2%. CONCLUSIONS: Mumps transmission control was inadequate to control the mumps outbreak. Although high inapparent infection rate would mitigate the transmission control effect of case isolation, this measure is fundamental for infection control. The reasons of this inadequate status need to be explored to develop an effective intervention strategy.
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OBJECTIVES This study was performed to examine medical care utilization of psychiatric patients and to explore patients' characteristics associated with extended hospitalization. METHODS: Data were extracted from information of Korean Health Insurance Review and Assessment Service. All data associated with admission and outpatient clinic visit were analysed by patient characteristics. We selected first psychiatric admission patients who diagnosed mental and behavioral disorders due to use of alcohol (main disease code: F10), schizophrenia and related disorders (F20-29) and mood disorders (F30~33) from January to June 2005. We analysed status of admission, mean length of stay, regular access to outpatient clinic and rates of extended hospitalization during 3 years. Bivariate and multivariate analyses were conducted to identify factors associated with extended hospitalization. RESULTS: The number of psychiatric patients during the first six month of 2005 was 30,678. The mean length of stay was longest for schizophrenia and related disorders but shortest for mood disorders. Patients who experienced an extended hospitalization were 18.8% of total subjects. An extended hospitalization was more common in schizophrenia and related disorders than other diagnostic groups. The factors associated with the extended hospitalization were age, sex, diagnostic group, type of insurance and medical care utilization groups. CONCLUSIONS: The study indicates the problem of an extended hospitalization for psychiatric patients in Korea. It is suggested that variations in rates of extended hospitalization among medical care utilization group may need an active early intervention system in psychiatric treatment service. Particular attention needs to be devoted to planning and funding for reducing extended hospitalization.
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