| 1. |
- 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. |
- Tjonneland, A., et al.
(författare)
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Linoleic acid, a dietary n-6 polyunsaturated fatty acid, and the aetiology of ulcerative colitis: a nested case-control study within a European prospective cohort study
- 2009
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 58:12, s. 1606-1611
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Dietary linoleic acid, an n-6 polyunsaturated fatty acid, is metabolised to arachidonic acid, a component of colonocyte membranes. Metabolites of arachidonic acid have pro-inflammatory properties and are increased in the mucosa of patients with ulcerative colitis. The aim of this investigation was to conduct the first prospective cohort study investigating if a high dietary intake of linoleic acid increases the risk of developing incident ulcerative colitis. Design and setting: Dietary data from food frequency questionnaires were available for 203 193 men and women aged 30-74 years, resident in the UK, Sweden, Denmark, Germany or Italy and participating in a prospective cohort study, the European Prospective Investigation into Cancer and Nutrition (EPIC). These participants were followed up for the diagnosis of ulcerative colitis. Each case was matched with four controls and the risk of disease calculated by quartile of intake of linoleic acid adjusted for gender, age, smoking, total energy intake and centre. Results: A total of 126 participants developed ulcerative colitis (47% women) after a median follow-up of 4.0 years (range, 1.7-11.3 years). The highest quartile of intake of linoleic acid was associated with an increased risk of ulcerative colitis (odds ratio (OR) = 2.49, 95% confidence interval (CI) = 1.23 to 5.07, p = 0.01) with a significant trend across quartiles (OR = 1.32 per quartile increase, 95% CI = 1.04 to 1.66, p = 0.02 for trend). Conclusions: The data support a role for dietary linoleic acid in the aetiology of ulcerative colitis. An estimated 30% of cases could be attributed to having dietary intakes higher than the lowest quartile of linoleic acid intake.
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| 4. |
- Salzer, Jonatan, 1981-, et al.
(författare)
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Epstein-Barr virus antibodies and vitamin D in prospective multiple sclerosis biobank sampels
- 2013
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 19:12, s. 1587-1591
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Tidskriftsartikel (refereegranskat)abstract
- Background: Increased antibody reactivity against Epstein-Barr Nuclear Antigen-1 (EBNA-1) has been associated with an increased risk for MS, and high levels of 25-Hydroxyvitamin D (25[OH]D) have been associated with a lower risk for MS. Interaction between these two factors has been proposed.Objectives: To examine the association between antibody reactivity against EBNA-1 and five EBNA-1 domains, and the risk for multiple sclerosis (MS), and to examine if these antibodies and 25(OH)D status interact regarding MS risk in prospectively collected blood samples.Methods: Antibody reactivity (as specified above) and 25(OH)D levels were measured using ELISAs in n=192 MS cases and n=384 matched controls. The risk for MS was analysed using matched logistic regression.Results: The risk for MS increased across tertiles of antibody reactivity against EBNA-1, domain EBNA-1402–502, and domain EBNA-1385–420; p trend <0.001. The risk increase was most pronounced for EBNA-1385–420. In young individuals (below median age at sampling, <26.4 years) these associations were stronger, and 25(OH)D levels correlated inversely to antibody reactivity against EBNA-1 and the EBNA-1 domains.Conclusions: We confirm that increased antibody reactivity against EBNA-1 is a risk factor for MS. Our findings in young individuals suggest that 25(OH)D status might influence the immune response towards Epstein-Barr virus, and thereby modulate MS risk.
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| 5. |
- Salzer, Jonatan, 1981-, et al.
(författare)
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Smoking as a risk factor for multiple sclerosis
- 2013
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 19:8, s. 1022-1027
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Tidskriftsartikel (refereegranskat)abstract
- Background: Smoking has been associated with an increased risk for multiple sclerosis, but no studies have measured levels of the nicotine metabolite cotinine in prospectively collected samples to assess exposure.Objective: To investigate the effects of laboratory defined tobacco use on the risk for multiple sclerosis using prospectively collected biobank blood samples.Methods: Levels of cotinine were measured in n=192 cases, and n=384 matched controls, using an immunoassay. The risk for multiple sclerosis was estimated using matched logistic regression.Results: Elevated cotinine levels (≥10 ng/ml) were associated with a significantly increased risk for multiple sclerosis, (odds ratio, OR 1.5, 95% confidence interval, CI 1.0–2.1). This association was only present in young individuals (below median age at blood sampling, <26.4 years), (OR 2.2, 95% CI 1.3–3.8).Conclusions: This study confirms that smoking is a risk factor for multiple sclerosis. It has the advantage of using analyses of cotinine levels in samples that were collected several years before disease onset, thus excluding any risk for recall bias and minimising the risk for reversed causation. Our results also suggest that the smoking related immunological events that contribute to the development of multiple sclerosis occur early in life.
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| 6. |
- Toniolo, Paolo, et al.
(författare)
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Human chorionic gonadotropin in pregnancy and maternal risk of breast cancer
- 2010
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 70:17, s. 6779-6786
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Tidskriftsartikel (refereegranskat)abstract
- Full-term pregnancies are associated with long-term reductions in maternal risk of breast cancer, but the biological determinants of the protection are unknown. Experimental observations suggest that human chorionic gonadotropin (hCG), a major hormone of pregnancy, could play a role in this association. A case-control study (242 cases and 450 controls) nested within the Northern Sweden Maternity Cohort included women who had donated a blood sample during the first trimester of a first full-term pregnancy. Total hCG was determined on Immulite 2000 analyzer. Odds ratios (OR) and 95% confidence intervals (CI) were estimated through conditional logistic regression. Maternal breast cancer risk decreased with increasing hCG (upper tertile OR, 0.67; CI, 0.46-0.99), especially for pregnancies before age 25 (upper tertile OR, 0.41; CI, 0.21-0.80). The association diverged according to age at diagnosis: risk was reduced after age 40 (upper tertile OR, 0.60; CI, 0.39-0.91) and seemed to increase before age 40 (upper tertile OR, 1.78; CI, 0.72-4.38). Risk was reduced among those diagnosed 10 years or longer after blood draw (upper tertile OR, 0.60; CI, 0.40-0.90), but not so among those diagnosed within 10 years (upper tertile OR, 4.33; CI, 0.86-21.7). These observations suggest that the association between pregnancy hCG and subsequent maternal risk of breast cancer is modified by age at diagnosis. Although the hormone seems to be a determinant of the reduced risk around or after age 50, it might not confer protection against, or it could even increase the risk of, cancers diagnosed in the years immediately following pregnancy.
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| 9. |
- Nordin, Elise, 1985, et al.
(författare)
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An inverse association between plasma benzoxazinoid metabolites and PSA after rye intake in men with prostate cancer revealed with a new method
- 2022
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322 .- 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer (PC) is a common cancer among men, and preventive strategies are warranted. Benzoxazinoids (BXs) in rye have shown potential against PC in vitro but human studies are lacking. The aim was to establish a quantitative method for analysis of BXs and investigate their plasma levels after a whole grain/bran rye vs refined wheat intervention, as well as exploring their association with PSA, in men with PC. A quantitative method for analysis of 22 BXs, including novel metabolites identified by mass spectrometry and NMR, was established, and applied to plasma samples from a randomized crossover study where patients with indolent PC (n = 17) consumed 485 g whole grain rye/rye bran or fiber supplemented refined wheat daily for 6 wk. Most BXs were significantly higher in plasma after rye (0.3–19.4 nmol/L in plasma) vs. refined wheat (0.05–2.9 nmol/L) intake. HBOA-glc, 2-HHPAA, HBOA-glcA, 2-HPAA-glcA were inversely correlated to PSA in plasma (p < 0.04). To conclude, BXs in plasma, including metabolites not previously analyzed, were quantified. BX metabolites were significantly higher after rye vs refined wheat consumption. Four BX-related metabolites were inversely associated with PSA, which merits further investigation.
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| 10. |
- Olsson, Jan, et al.
(författare)
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Time trends in herpesvirus seroepidemiology among Swedish adults
- 2024
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Ingår i: BMC Infectious Diseases. - : Springer Nature. - 1471-2334. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Human herpesviruses are widespread among the human population. The infections often occurunnoticed, but severe disease as well as long-term sequelae are part of the symptom spectrum. The prevalence variesamong subpopulations and with time. The aim of this study was to describe the seroprevalence of ImmunoglobulinG against Herpes simplex 1, Herpes simplex 2, Epstein-Barr virus and Cytomegalovirus in the adult Swedish populationover a time period of several decades.Methods: Serum samples (n = 892) from biobanks, originating from 30-year-old women, 50-year-old menand 50-year-old women sampled between 1975 and 2018, were analyzed for presence of anti-herpesvirus antibod-ies. Linear regression analysis was used to test for a correlation between birth year and seroprevalence. Multiple linearregression analysis was used to differentiate between other factors such as age and gender.Results: Birth year correlated negatively with the prevalence of immunoglobulin G against Herpes simplex 1and Epstein-Barr virus (p = 0.004 and 0.033), and positively with Immunoglobulin G against Cytomegalovirus(p = 0.039). When participant categories were analyzed separately, birth year correlated negatively with the preva-lence of Immunoglobulin G against Herpes simplex 1 and Herpes simplex 2 (p = 0.032 and 0.028) in 30-year-old women,and with the prevalence of Immunoglobulin G against Cytomegalovirus in 50-year-old men (p = 0.011).Conclusions: The prevalence of Immunoglobulin G against Herpes simplex 1, Herpes simplex 2 and Epstein-Barr virusdecreases in later birth cohorts. This indicates a trend of declining risk of getting infected with these viruses as a childand adolescen (9) (PDF) Time trends in herpesvirus seroepidemiology among Swedish adults.
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