The ATBC Study was a randomized, double-blind, placebo-controlled, 2x2 factorial design trial primarily testing the hypothesis that α-tocopherol and ß-carotene supplements reduce the incidence of lung and other cancers. From 1985 to 1988, 29 133 male smokers (5 cigarettes per day) from the total male population aged 50 to 69 years of southwestern Finland (n=290 406) were recruited and randomized to 1 of 4 intervention regimens: α-tocopherol alone at 50 mg per day, ß-carotene alone at 20 mg per day, α-tocopherol plus ß-carotene, or placebo. Potential participants with a history of cancer or serious illness limiting long-term participation, those taking supplements of vitamin E, vitamin A, or ß-carotene in excess of predefined doses, and those being treated with anticoagulants were excluded.
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National Public Health Institute-dedicated to preserve
national DNA resources for common good
To guarantee the top level of expertise in modern genetic and biological analyses, we have built an infrastructure that facilitates the collection of genome-wide information on the genetic background of diseases as well as functional information on the molecules that are critical in the disease process. Furthermore we have established the necessary storage, database and computational resources for the expert analyses of the massive amount of collected biological information. Our scientific expertise, technology platforms and large nationwide sample collections facilitate a highly competitive environment for research and education in molecular medicine of the 21st century.
The biobanking wet lab effort is concentrated to KTL/Biomedicum Large scale DNA extraction and storage facility. The facility presently houses DNA from more than 200 000 individuals and is co-ordinated by National Public Health Institute. It is equipped with state of the art bar coding system for sample tracking, an automated Gentra DNA extraction equipment, liquid handling robots, storage facilities, and tailor made data management tools for optimal confidentiality and quality control.
FINRISK
FINRISK, a set of cohorts from Finland The cohorts comprise the respondents of cross-sectional population surveys that were carried out to assess especially the coronary risk factors and health behaviour in the working age population in several geographically defined areas of Finland in 1992, 1997 and 2002 using the MONICA protocol (cf. MORGAM). DNA samples were collected, and a wide spectrum of laboratory tests were carried out from serum and plasma, which are still available from the 1997 and 2002 cohorts. The cohort sizes are 5999 men and women in 1992, 8141 in 1997 and 8799 in 2002. The cohorts have been followed up by linking them to the national hospital discharge register, causes-of-death register and cancer register
Health2000
Health 2000 was a health interview and examination survey carried out in Finland from fall 2000 to spring 2001. KTL (National Public Health Institute) had the main responsibility for the survey. Also other Finnish social and health care organizations participated. The main partners comprise KTL and the Central Pension Institute, the Social Insurance Institution, the Municipal Pension Institute, Statistics Finland, The National Research and Development Centre for Welfare and Health, the Institute of Occupational Health and the UKK-institute for Health Promotion. The Social Insurance Institution carried out a comparable study 20 years ago called Mini-Finland health survey. Please see chapter 9 for more detailed description of the Mini-Finland-study. The main aim of Health 2000 is to provide an up-to-date comprehensive picture of health and functional ability in the working-aged and aged population by studying the prevalence and determinants of most important health problems and associated need for care, rehabilitation and help. A nationally representative sample of 10,000 persons was drawn of the population aged 18 and over. Targets of the study are general health, major chronic conditions, functional ability and limitations, determinants of health, health needs and service needs and their satisfaction.
The Helsinki Sudden Death Study (HSDS)
The Helsinki Sudden Death Study (HSDS) was launched to study the lifestyle and genetic factors predisposing to sudden death in Finnish middle-aged men who lived in Helsinki and its surroundings. The HSDS consists of 2 autopsy series collected at 10-year intervals. The first series (A series) was collected during 1981-1982 and the second series (B series) during 1991-1992. The 2 autopsy series included 700 men 33 to 70 years old (mean 53.07 years, SD 9.58 years, median 54 years) subjected to a medicolegal autopsy. Indications for an autopsy were out-of-hospital death of a previously healthy man, accidental death, suspected intoxication, suicide, or death in connection with medical treatment. More than half the men died of disease, 68% of cardiac origin. The second most common causes of death were intoxication and violence, most of these accidental or self-inflicted.
Birth cohorts from Northern Finland
Birth cohorts from Northern Finland: Two birth cohorts collected from the Northern part of Finland134: The 1966 cohort (NFBC 1966) ascertained 12058 live births to mothers in the northernmost two provinces of Finland and the 1986 cohort (NFBC 1986) ascertained 9432 births. Pregnancies were followed prospectively from the first antenatal contact (10-16th week), and the offspring then examined at birth, 1y, 7-8y (1986 only), 14-16y and, in the case of the 1966 cohort, at 31y. At these time points, a wide range of phenotypic, lifestyle, demographic and other data were gathered using both questionnaires and clinical examinations. The NFBCs provide possibly the world’s largest data on early pregnancy measures with follow up until age 40y. In addition, linkage to national registries (hospitalization, deaths, education, medication, pensions) has provided (and continues to provide) access to additional sources of demographic and biological data. DNA samples are available for 5900 subjects of NFBC 1966 and 6700 subjects of NFBC1986. These “Oulu cohorts” have extensive data for intermediate phenotypes with established relevance to obesity related and behavioural traits, and include extensive quantitative information on substance use, particularly that of tobacco and alcohol, but also including data on drugs of abuse.
Finnish Twin Cohort
The Finnish Twin Cohort: The Finnish Twin Cohort142 was first established in 1974 to investigate genetic and environmental risk factors for chronic disorders. Twins and their families have been ascertained in three stages from the Central Population Register in 1974 (older like-sexed pairs), 1987 (multiple births 1968-1987) and 1995 (opposite-sex pairs 1938-1957), with a total of 3500 pairs with both members currently alive. The older part consists of same gender twin pairs born before 1958 with both twins alive in 1975, and three surveys have been carried out in 1975, 1981 and 1990 with the response rates varying between 77 and 89%. A major part of the study information is collected by questionnaires. This data and registry follow-up has directed many following substudies concentrating more specifically for different phenotypes. In addition to mortality follow-up, morbidity follow-up of the twins has been performed through nationwide computerized medical registries: incident malignancies through the Cancer registry, hospitalisations through the Hospital Discharge Register, disability pension information and information of selected diseases based on the national register for fully-reimbursable medications. Numerous subsample studies have been performed, with DNA collection a routine feature since the mid 1990s. For the younger cohort, two five year birth cohorts born 1975-1979 & 1983-1987 have been studied in a intensive longitudinal manner. Together they compromise about 5500 families with twins (twins, parents and sibs), who have participated in four (1975-79 twins) or three (1983-87 twins) waves of questionnaires & interviews with more intense subset studies, including DNA collection. The fourth wave of data collection for the youngest twins including a clinical assessment and blood sample collection starts in late 2005. Among the intensively studies subsamples are studies that have examined pairs and families with obesity, hypertension, smoking, osteoarthritis, migraine, alcohol use, physical inactivity and fitness, dementia, eating disorders, and low back pain risk factors. Over 13 000 DNA samples have been collected, and serum is available from several substudies as well.
Family Studies
Finnish family studies: The Finnish population is unique among the Caucasian populations due to its long lasting linguistic and geographical isolation. The present population was founded by perhaps only a few hundred settlers who arrived to Finland around 2000 years ago on the southern coast of the country. Later the population underwent several bottlenecks and northern and eastern parts of the country were populated relatively late in the 17th century, resulting in further internal isolates with a well established bottle neck effects having significant impact on the LD intervals in rare and common alleles. Migration within the country was rare until 1950ies and immigration has been almost non-existent. Although marriages among relatives are rare in Finland the internal isolation of villages and other communities has resulted in”megafamilies” having several loops. Such loops can easily be identified with the help of the Finnish Church records, which reach back to the late 17th century. The existence of internal isolates is still a reality, with the country still sparsely populated, and only 5 million people living on a surface area similar to the state of California. A total of 2800 multiplex families with DNA from 14 600 individuals is available. A 400 or 800 marker genome scan has been performed from 4500 individuals.
GenomEUtwin
Major International Projects Biobanked at KTL - GenomEUtwin This project will apply and develop new molecular and statistical strategies to analyze unique European twin and other population cohorts to define and characterise the genetic, environmental and life-style components in the background of health problems like obesity, migraine, coronary heart disease and stroke, representing major health care problems worldwide. The participating 8 twin cohorts form an amazing collection of over 0.6 million pairs of twins. Tens of thousands of DNA samples with informed consents for genetic studies of common diseases have already been stored from these population-based twin cohorts. Just as the twin studies, the WHO MONICA (www.ktl.fi/monica) collaboration has a long and successful history of conducting multicentre research, which makes it ideal for embarking on genetic studies of complex, multifactorial diseases. These unique study samples will be analysed in four intellectual core facilities of this integrated project using accumulated expertise by partners in genetics, epidemiology and biostatistics.
GEHA
GEHA –Genetics of Healthy Aging - The aim of the Integrated Project (IP) GEHA is to identify genes involved in healthy aging and longevity, which allow individuals to survive to advanced old age in good cognitive and physical function and in the absence of major age-related diseases. To achieve this aim a coherent, tightly integrated program of research that unites demographers, geriatricians, geneticists, genetic epidemiologists, molecular biologists, bioinfomaticians and statisticians has been set up. The genetic analysis will be performed by 9 high throughput platforms, within the framework of a centralized database. The working plan of this IP is to collect an unprecedented number (2650) of long-lived (90+) sibpairs from 11 European whose DNA will be stored at KTL.
MORGAM
MORGAM is a pooling project based on cohorts which were originally recruited for population surveys carried out by the WHO MONICA Project centres during the 1980s and 1990s. Today the study extends to 20 centres in 11 countries and 143296 subjects in the cohorts with a total of 14054 deaths, and 9499 first fatal or non–fatal coronary heart disease (CHD) or stroke events during prospective follow-up. DNA are available for 69 266 of these subjects, with a total of 4824 deaths and 4296 first fatal and non-fatal CHD and Stroke events. Considerable energy has been expended on ensuring phenotypic and endpoint comparability. This has been achieved by means of the application of strict quality control and assessment procedures. The MORGAM strategy has been to measure limited range of well-standardised phenotypes and to relate these eventually to a large number of genotypes. The phenotypes include the classic cardiovascular risk factors and height, weight, BMI and waist/hip ratio which are of special interest to insulin resistance. Serum is still available from many of the cohorts for in-depth assessment of biomarkers. MORGAM has adopted a case cohort design for the genotyping. This allows for the study of multiple endpoints and also establishes gene frequency in the different participating populations. MORGAM is examining the effects of population stratification in multinational cohort studies and developing strategies for analysing the wealth of data which is accumulating. MORGAM has also had to develop its own rules to cope with the ethical issues which are involved in studies of its type.
