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- Burgess, S., et al.
(författare)
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Bayesian methods for meta-analysis of causal relationships estimated using genetic instrumental variables
- 2010
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Ingår i: Statistics in medicine. - : Wiley. - 1097-0258 .- 0277-6715. ; 29:12, s. 1298-311
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Tidskriftsartikel (refereegranskat)abstract
- Genetic markers can be used as instrumental variables, in an analogous way to randomization in a clinical trial, to estimate the causal relationship between a phenotype and an outcome variable. Our purpose is to extend the existing methods for such Mendelian randomization studies to the context of multiple genetic markers measured in multiple studies, based on the analysis of individual participant data. First, for a single genetic marker in one study, we show that the usual ratio of coefficients approach can be reformulated as a regression with heterogeneous error in the explanatory variable. This can be implemented using a Bayesian approach, which is next extended to include multiple genetic markers. We then propose a hierarchical model for undertaking a meta-analysis of multiple studies, in which it is not necessary that the same genetic markers are measured in each study. This provides an overall estimate of the causal relationship between the phenotype and the outcome, and an assessment of its heterogeneity across studies. As an example, we estimate the causal relationship of blood concentrations of C-reactive protein on fibrinogen levels using data from 11 studies. These methods provide a flexible framework for efficient estimation of causal relationships derived from multiple studies. Issues discussed include weak instrument bias, analysis of binary outcome data such as disease risk, missing genetic data, and the use of haplotypes.
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| 2. |
- Engström, Gunnar, et al.
(författare)
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The Swedish CArdioPulmonary BioImage Study : objectives and design
- 2015
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 278:6, s. 645-659
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Tidskriftsartikel (refereegranskat)abstract
- Cardiopulmonary diseases are major causes of death worldwide, but currently recommended strategies for diagnosis and prevention may be outdated because of recent changes in risk factor patterns. The Swedish CArdioPulmonarybioImage Study (SCAPIS) combines the use of new imaging technologies, advances in large-scale 'omics' and epidemiological analyses to extensively characterize a Swedish cohort of 30 000 men and women aged between 50 and 64 years. The information obtained will be used to improve risk prediction of cardiopulmonary diseases and optimize the ability to study disease mechanisms. A comprehensive pilot study in 1111 individuals, which was completed in 2012, demonstrated the feasibility and financial and ethical consequences of SCAPIS. Recruitment to the national, multicentre study has recently started.
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| 3. |
- Pukkala, Eero, et al.
(författare)
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Nordic biological specimen banks as basis for studies of cancer causes and control - more than 2 million sample donors, 25 million person years and 100 000 prospective cancers
- 2007
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 46:3, s. 286-307
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Tidskriftsartikel (refereegranskat)abstract
- The Nordic countries have a long tradition of large-scale biobanking and comprehensive, population-based health data registries linkable on unique personal identifiers, enabling follow-up studies spanning many decades. Joint Nordic biobank-based studies provide unique opportunities for longitudinal molecular epidemiological research. The purpose of the present paper is to describe the possibilities for such joint studies, by describing some of the major Nordic biobank cohorts with a standardised calculation of the cancer incidence in these cohorts. Altogether two million donors have since 1966 donated more than four million biological samples, stored at -20 degrees C to -135 degrees C, to 17 biobank cohorts in Finland, Iceland, Norway and Sweden. As a result of joint database handling principles, the accuracy of personal identifiers and completeness of follow-up for vital status in all participating biobanks was improved. Thereafter, the cancer incidence was determined using follow-up through the national cancer registries. Biobanks based on random samples of population typically showed slightly lower cancer incidence rates than the general population, presumably due to better participation rates among health-conscious subjects. On the other hand, biobanks including samples for viral screening or clinical testing showed 1.5 to 2.1 fold increased incidence of cancer. This excess was very high immediately after sampling, but for some cancer sites remained elevated for years after clinical sampling. So far, more than 100 000 malignant neoplasms have occurred after sample donation, and the annual increase of the cancer cases in these cohorts is about 10 000. The estimates on the population-representativity of the biobanks will assist in interpretation of generalizability of results of future studies based on these samples, and the systematic tabulations of numbers of cancer cases will serve in study power estimations. The present paper summarizes optimal study designs of biobank-based studies of cancer.
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| 8. |
- Bamia, C, et al.
(författare)
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Dietary patterns among older Europeans: the EPIC-Elderly study
- 2005
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Ingår i: British Journal of Nutrition. - 1475-2662 .- 0007-1145. ; 94:1, s. 100-113
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Tidskriftsartikel (refereegranskat)abstract
- Overall dietary patterns have been associated with health and longevity. We used principal component (PC) and cluster analyses to identify the prevailing dietary patterns of 99 744 participants, aged 60 years or older, living in nine European countries and participating in the European Prospective Investigation into Cancer and Nutrition (EPIC-Elderly cohort) and to examine their socio-demographic and lifestyle correlates. Two PC were identified: PC1 reflects a 'vegetable-based' diet with an emphasis on foods of plant origin, rice, pasta and other grain rather than on margarine, potatoes and non-alcoholic beverages. PC2 indicates a 'sweet- and fat-dominated' diet with a preference for sweets, added fat and dairy products but not meat, alcohol, bread and eggs. PC1 was associated with a younger age, a higher level of education, physical activity, a higher BMI, a lower waist:hip ratio and never and past smoking. PC2 was associated with older age, less education, never having smoked, a lower BMI and waist:hip ratio and lower levels of physical activity. Elderly individuals in southern Europe scored positively on PC1 and about zero on PC2, whereas the elderly in northern Europe scored negatively on PC1 and variably on PC2. The results of cluster analysis were compatible with the indicated dietary patterns. 'Vegetable-based' and a 'sweet- and fat-dominated' diets are prevalent among the elderly across Europe, and there is a north-south gradient regarding their dietary choices. Our study contributes to the identification of groups of elderly who are likely to have different prospects for long-term disease occurrence and survival.
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| 9. |
- Bergström, Göran, 1964, et al.
(författare)
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Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population
- 2021
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Ingår i: Circulation. - Philadelphia : American Heart Association. - 0009-7322 .- 1524-4539. ; 144:12, s. 916-929
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Tidskriftsartikel (refereegranskat)abstract
- Background: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population.Methods: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or ≥50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data.Results: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (≥50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population.Conclusions: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk.
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| 10. |
- Bergström, Göran, et al.
(författare)
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Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population
- 2021
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Ingår i: Circulation. - : Wolters Kluwer. - 0009-7322 .- 1524-4539. ; 144:12, s. 916-929
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Tidskriftsartikel (refereegranskat)abstract
- Background: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population.Methods: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or ≥50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data.Results: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (≥50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population.Conclusions: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk.
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