| 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. |
- Andersson, Jonas, 1977-, et al.
(författare)
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Effects of heavy endurance physical exercise on inflammatory markers in non-athletes
- 2010
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 209:2, s. 601-605
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Physical activity has beneficial effects on cardiovascular disease but the mechanisms are still somewhat unclear. One possible pathway may be through the anti-inflammatory effects attributed to regular physical activity. Our primary aim was to study the effects of endurance physical exercise on C-reactive protein (CRP), Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNFalpha) during the acute and recovery phases. Secondarily, we studied the impact of diet on these inflammatory markers.METHODS: Twenty men, aged 18-55 years, participated in a 14 days cross-country skiing tour. They traveled 12-30km per day corresponding to about 10h of heavy physical activity. The participants were randomized to a diet with either 30 or 40% of energy derived from fat. Inflammatory variables were analysed at week 0, after 1 and 2 weeks and during the recovery phase at week 6 and 8.RESULTS: CRP and TNFalpha increased significantly during the two weeks of exercise (1.4-5.0mg/l, p=0.00 and 6.8-8.4pg/ml, p=0.00). CRP levels were significantly lower during recovery (median 0.7mg/l) compared to baseline (median 1.4mg/l) and did not correlate to metabolic variables. There were no significant changes in IL-6 levels during the study period. For dietary groups significant CRP changes were observed only in the high fat group during recovery.CONCLUSIONS: CRP and TNFalpha increased significantly but reacted differently during heavy physical activity while there seemed to be no significant changes in IL-6. No significant differences regarding inflammatory variables were found between the dietary groups.
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| 3. |
- Erzurumluoglu, A. Mesut, et al.
(författare)
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Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci
- 2020
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Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 25:10, s. 2392-2409
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Tidskriftsartikel (refereegranskat)abstract
- Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations with P < 5 × 10-8 in either analysis were taken forward for replication in up to 275,596 independent participants from UK Biobank. Lastly, a meta-analysis of the discovery and replication studies was performed. Sixteen SNVs were associated with at least one of the smoking behaviour traits (P < 5 × 10-8) in the discovery samples. Ten novel SNVs, including rs12616219 near TMEM182, were followed-up and five of them (rs462779 in REV3L, rs12780116 in CNNM2, rs1190736 in GPR101, rs11539157 in PJA1, and rs12616219 near TMEM182) replicated at a Bonferroni significance threshold (P < 4.5 × 10-3) with consistent direction of effect. A further 35 SNVs were associated with smoking behaviour traits in the discovery plus replication meta-analysis (up to 622,409 participants) including a rare SNV, rs150493199, in CCDC141 and two low-frequency SNVs in CEP350 and HDGFRP2. Functional follow-up implied that decreased expression of REV3L may lower the probability of smoking initiation. The novel loci will facilitate understanding the genetic aetiology of smoking behaviour and may lead to the identification of potential drug targets for smoking prevention and/or cessation.
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| 4. |
- Nilsson, Lena Maria, et al.
(författare)
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Low-carbohydrate, high-protein score and mortality in a northern Swedish population-based cohort.
- 2012
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Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 0954-3007 .- 1476-5640. ; 66:6, s. 694-700
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/OBJECTIVE: Long-term effects of carbohydrate-restricted diets are unclear. We examined a low-carbohydrate, high-protein (LCHP) score in relation to mortality. SUBJECTS/METHODS: This is a population-based cohort study on adults in the northern Swedish county of Va¨sterbotten. In 37 639 men (1460 deaths) and 39 680 women (923 deaths) from the population-based Va¨sterbotten Intervention Program, deciles of energy-adjusted carbohydrate (descending) and protein (ascending) intake were added to create an LCHP score (2 --20 points). Sex-specific hazard ratios (HR) were calculated by Cox regression. RESULTS: Median intakes of carbohydrates, protein and fat in subjects with LCHP scores 2--20 ranged from 61.0% to 38.6%, 11.3% to 19.2% and 26.6% to 41.5% of total energy intake, respectively. High LCHP score (14 --20 points) did not predict all-cause mortality compared with low LCHP score (2 --8 points), after accounting for saturated fat intake and established risk factors (men: HR for high vs low 1.03 (95% confidence interval (CI) 0.88 -- 1.20), P for continuous¼0.721; women: HR for high vs low 1.10 (95% CI 0.91 -- 1.32), P for continuous¼0.229). For cancer and cardiovascular disease, no clear associations were found. Carbohydrate intake was inversely associated with all-cause mortality, though only statistically significant in women (multivariate HR per decile increase 0.95 (95% CI 0.91 -- 0.99), P¼0.010). CONCLUSION: Our results do not support a clear, general association between LCHP score and mortality. Studies encompassing a wider range of macronutrient consumption may be necessary to detect such an association.
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| 5. |
- Warensjö, Eva, et al.
(författare)
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Biomarkers of milk fat and the risk of myocardial infarction in men and women : a prospective, matched case-control study
- 2010
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 92:1, s. 194-202
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Tidskriftsartikel (refereegranskat)abstract
- Background: High intakes of saturated fat have been associated with cardiovascular disease, and milk fat is rich in saturated fat. Objective: The objective of this study was to investigate the association between the serum milk fat biomarkers pentadecanoic acid (15:0), heptadecanoic acid (17:0), and their sum (15:0+17:0) and a first myocardial infarction (MI). Design: The study design was a prospective case-control study nested within a large population- based cohort in Sweden. Included in the study were 444 cases (307 men) and 556 controls (308 men) matched on sex, age, date of examination, and geographic region. Clinical, anthropometric, biomarker fatty acid, physical activity, and dietary data were collected. The odds of a first MI were investigated by using conditional logistic regression. Results: In women, proportions of milk fat biomarkers in plasma phospholipids were significantly higher (P < 0.05) in controls than in cases and were, in general, negatively, albeit weakly, correlated with risk factors for metabolic syndrome. The crude standardized odds ratios of becoming an MI case were 0.74 (95% CI: 0.58, 0.94) in women and 0.91 (95% CI: 0.77, 1.1) in men. After multivariable adjustment for confounders, the inverse association remained in both sexes and was significant in women. In agreement with biomarker data, quartiles of reported intake of cheese (men and women) and fermented milk products (men) were inversely related to a first MI (P for trend < 0.05 for all). Conclusions: Milk fat biomarkers were associated with a lower risk of developing a first MI, especially in women. This was partly confirmed in analysis of fermented milk and cheese intake. Components of metabolic syndrome were observed as potential intermediates for the risk relations. Am J Clin Nutr 2010; 92:194-202.
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| 6. |
- Wennberg, Patrik, 1972-, et al.
(författare)
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Reduced risk of myocardial infarction related to active commuting : inflammatory and haemostatic effects are potential major mediating mechanisms
- 2010
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Ingår i: European Journal of Cardiovascular Prevention & Rehabilitation. - 1741-8267 .- 1741-8275. ; 17:1, s. 56-62
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Regular physical activity is inversely associated with risk of coronary heart disease, but the precise mechanisms remain unclear. Active commuting is an environmental friendly way to achieve the recommended 30 min of daily physical activity. The aim of this study was to explore the relative contribution of markers from different potential mediating pathways on the association between active commuting and risk of myocardial infarction (MI) in a general population. DESIGN: Prospective incident nested case-control study. METHODS: Commuting habits, traditional risk factors and biomarkers were assessed at baseline and compared in 204 MI cases and 327 matched controls. RESULTS: Car commuting was significantly associated with MI risk, even after adjusting for potential confounders (odds ratio: 1.77, 95% confidence interval: 1.05-2.99). When potential mediators were included in the model, the risk was substantially attenuated. Among the traditional risk factors, apolipoprotein B/apolipoprotein A-1 ratio seemed to be the largest mediator (26.0%), followed by body mass index (18.7%). The inflammatory and haemostatic markers similarly dampened the effect, with tissue plasminogen activator/plasminogen activator inhibitor-1 complex and IL-6 explaining 33.6 and 27.6% of MI risk, respectively. Combined, the potential mediators investigated seemed to explain 40.1% of MI risk related to car commuting. CONCLUSION: Overall, the traditional, inflammatory and haemostatic markers seemed to explain a substantial proportion of the reduction in MI risk related to active commuting in this study population. The predominant effect of the inflammatory and haemostatic markers supports the hypothesis that regular physical activity may work through additional biological mechanisms to reduce coronary risk beyond traditional risk factors. However, these findings need to be confirmed in larger studies.
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| 7. |
- Wiklund, Peder, et al.
(författare)
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Abdominal and gynoid adipose distribution and incident myocardial infarction in women and men
- 2010
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Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 34:12, s. 1752-1758
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Tidskriftsartikel (refereegranskat)abstract
- In summary, fat distribution was a strong predictor of the risk of MI in women, but not in men. These different results may be explained by the associations found between fat distribution and hypertension, impaired glucose tolerance and hypertriglyceridemia.
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