| 1. |
- Hop, Paul J., et al.
(författare)
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Genome-wide study of DNA methylation shows alterations in metabolic, inflammatory, and cholesterol pathways in ALS
- 2022
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science. - 1946-6234 .- 1946-6242. ; 14:633
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Tidskriftsartikel (refereegranskat)abstract
- Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an estimated heritability between 40 and 50%. DNA methylation patterns can serve as proxies of (past) exposures and disease progression, as well as providing a potential mechanism that mediates genetic or environmental risk. Here, we present a blood-based epigenome-wide association study meta-analysis in 9706 samples passing stringent quality control (6763 patients, 2943 controls). We identified a total of 45 differentially methylated positions (DMPs) annotated to 42 genes, which are enriched for pathways and traits related to metabolism, cholesterol biosynthesis, and immunity. We then tested 39 DNA methylation-based proxies of putative ALS risk factors and found that high-density lipoprotein cholesterol, body mass index, white blood cell proportions, and alcohol intake were independently associated with ALS. Integration of these results with our latest genome-wide association study showed that cholesterol biosynthesis was potentially causally related to ALS. Last, DNA methylation at several DMPs and blood cell proportion estimates derived from DNA methylation data were associated with survival rate in patients, suggesting that they might represent indicators of underlying disease processes potentially amenable to therapeutic interventions.
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| 2. |
- Joost, Hans-Georg, et al.
(författare)
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Personalised nutrition : status and perspectives
- 2007
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Ingår i: British Journal of Nutrition. - 1475-2662. ; 98:01, s. 26-31
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Forskningsöversikt (refereegranskat)abstract
- Personalised, genotype-based nutrition is a concept that links genotyping with specific nutritional advice in order to improve the prevention of nutrition-associated, chronic diseases. This review describes the current scientific basis of the concept and discusses its problems. There is convincing evidence that variant genes may indeed determine the biological response to nutrients. The effects of single-gene variants on risk or risk factor levels of a complex disease are, however, usually small and sometimes inconsistent. Thus, information on the effects of combinations of relevant gene variants appears to be required in order to improve the predictive precision of the genetic information. Furthermore, very few associations between genotype and response have been tested for causality in human intervention studies, and little is known about potential adverse effects of a genotype-derived intervention. These issues need to be addressed before genotyping can become an acceptable method to guide nutritional recommendations.
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| 3. |
- Livingstone, Katherine M., et al.
(författare)
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FTO genotype and weight loss : systematic review and meta-analysis of 9563 individual participant data from eight randomised controlled trials
- 2016
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Ingår i: BMJ: British Medical Journal. - : BMJ. - 1756-1833. ; 354
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To assess the effect of the FTO genotype on weight loss after dietary, physical activity, or drug based interventions in randomised controlled trials.DESIGN: Systematic review and random effects meta-analysis of individual participant data from randomised controlled trials.DATA SOURCES: Ovid Medline, Scopus, Embase, and Cochrane from inception to November 2015.ELIGIBILITY CRITERIA FOR STUDY SELECTION: Randomised controlled trials in overweight or obese adults reporting reduction in body mass index, body weight, or waist circumference by FTO genotype (rs9939609 or a proxy) after dietary, physical activity, or drug based interventions. Gene by treatment interaction models were fitted to individual participant data from all studies included in this review, using allele dose coding for genetic effects and a common set of covariates. Study level interactions were combined using random effect models. Metaregression and subgroup analysis were used to assess sources of study heterogeneity.RESULTS: We identified eight eligible randomised controlled trials for the systematic review and meta-analysis (n=9563). Overall, differential changes in body mass index, body weight, and waist circumference in response to weight loss intervention were not significantly different between FTO genotypes. Sensitivity analyses indicated that differential changes in body mass index, body weight, and waist circumference by FTO genotype did not differ by intervention type, intervention length, ethnicity, sample size, sex, and baseline body mass index and age category.CONCLUSIONS: We have observed that carriage of the FTO minor allele was not associated with differential change in adiposity after weight loss interventions. These findings show that individuals carrying the minor allele respond equally well to dietary, physical activity, or drug based weight loss interventions and thus genetic predisposition to obesity associated with the FTO minor allele can be at least partly counteracted through such interventions.SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015015969.
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| 4. |
- Shannon, Oliver M., et al.
(författare)
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Mediterranean diet adherence and cognitive function in older UK adults : the European Prospective Investigation into Cancer and Nutrition-Norfolk (EPIC-Norfolk) Study
- 2019
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Ingår i: American Journal of Clinical Nutrition. - : HighWire Press. - 0002-9165 .- 1938-3207. ; 110:4, s. 938-948
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In Mediterranean countries, adherence to a traditional Mediterranean dietary pattern (MedDiet) is associated with better cognitive function and reduced dementia risk. It is unclear if similar benefits exist in non-Mediterranean regions.OBJECTIVES: The aims of this study were to examine associations between MedDiet adherence and cognitive function in an older UK population and to investigate whether associations differed between individuals with high compared with low cardiovascular disease (CVD) risk.METHODS: We conducted an analysis in 8009 older individuals with dietary data at Health Check 1 (1993-1997) and cognitive function data at Health Check 3 (2006-2011) of the European Prospective Investigation into Cancer and Nutrition-Norfolk (EPIC-Norfolk). Associations were explored between MedDiet adherence and global and domain-specific cognitive test scores and risk of poor cognitive performance in the entire cohort, and when stratified according to CVD risk status.RESULTS: Higher MedDiet adherence defined by the Pyramid MedDiet score was associated with better global cognition (β ± SE = -0.012 ± 0.002; P < 0.001), verbal episodic memory (β ± SE = -0.009 ± 0.002; P < 0.001), and simple processing speed (β ± SE = -0.002 ± 0.001; P = 0.013). Lower risk of poor verbal episodic memory (OR: 0.784; 95% CI: 0.641, 0.959; P = 0.018), complex processing speed (OR: 0.739; 95% CI: 0.601, 0.907; P = 0.004), and prospective memory (OR: 0.841; 95% CI: 0.724, 0.977; P = 0.023) was also observed for the highest compared with the lowest Pyramid MedDiet tertiles. The effect of a 1-point increase in Pyramid score on global cognitive function was equivalent to 1.7 fewer years of cognitive aging. MedDiet adherence defined by the Mediterranean Diet Adherence Screener (MEDAS) score (mapped through the use of both binary and continuous scoring) showed similar, albeit less consistent, associations. In stratified analyses, associations were evident in individuals at higher CVD risk only (P < 0.05).CONCLUSIONS: Higher adherence to the MedDiet is associated with better cognitive function and lower risk of poor cognition in older UK adults. This evidence underpins the development of interventions to enhance MedDiet adherence, particularly in individuals at higher CVD risk, aiming to reduce the risk of age-related cognitive decline in non-Mediterranean populations.
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| 5. |
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| 6. |
- Bergmann, Manuela M., et al.
(författare)
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Bioethical considerations for human nutrigenomics
- 2008
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Ingår i: Annual Review of Nutrition. - : Annual Reviews. - 0199-9885 .- 1545-4312. ; 28, s. 447-467
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Forskningsöversikt (refereegranskat)abstract
- This article gives an overview of the ethical issues in nutrigenomics; research and personalized nutrition. The principles of research ethics, i.e., autonomy, beneficence, nonmalfeasance, and justice, are challenged by rapidly growing cross-border research activities utilizing existing and upcoming biobanks for studies of the interaction of genes with diet on risk of common diseases. We highlight the ethical issues, some unresolved, in international collaborative projects of which researchers should be aware. Personalized nutrition (tailoring diet on the basis of genotype) is one possible application of nutrigenomics research. However, until the scientific evidence concerning diet-gene interactions is much more robust, the provision of personalized dietary advice on the basis of specific genotype remains questionable. From the ethical and social perspective, nutrigenomics offers significant opportunities to improve public health by enhancing understanding of the mechanisms through which diet can be used to reduce the risk of common polygenic diseases.
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| 7. |
- Görman, Ulf, et al.
(författare)
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Do we know enough? A scientific and ethical analysis of the basis for genetic-based personalized nutrition
- 2013
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Ingår i: Genes & Nutrition. - : Springer Science and Business Media LLC. - 1555-8932 .- 1865-3499. ; 8:4, s. 373-381
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Forskningsöversikt (refereegranskat)abstract
- This article discusses the prospects and limitations of the scientific basis for offering personalized nutrition advice based upon individual genetic information. Two divergent scientific positions are presented, with an ethical comment. The crucial question is whether the current knowledge base is sufficiently strong for taking an ethically responsible decision to offer personalized nutrition advice based upon gene–diet–health interaction. According to the first position, the evidence base for translating the outcomes of nutrigenomics research into personalized nutritional advice is as yet immature. There is also limited evidence that genotype-based dietary advice will motivate appropriate behavior changes. Filling the gaps in our knowledge will require larger and better randomized controlled trials. According to the second position, personalized nutrition must be evaluated in relation to generally accepted standard dietary advice—partly derived from epidemiological observations and usually not proven by clinical trials. With personalized nutrition, we cannot demand stronger evidence. In several specific cases of gene–diet interaction, it may be more beneficial for individuals with specific genotypes to follow personalized advice rather than general dietary recommendations. The ethical comment, finally, considers the ethical aspects of deciding how to proceed in the face of such uncertainty. Two approaches for an ethically responsible way forward are proposed. Arguing from a precautionary approach, it is suggested that personalized dietary advice should be offered only when there is strong scientific evidence for health effects, followed by stepwise evaluation of unforeseen behavioral and psychological effects. Arguing from theoretical and applied ethics as well as psychology, it is also suggested that personalized advice should avoid paternalism and instead focus on supporting the autonomous choice of each person.
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| 8. |
- Shannon, Oliver M., et al.
(författare)
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Mediterranean diet adherence is associated with lower dementia risk, independent of genetic predisposition : findings from the UK Biobank prospective cohort study
- 2023
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Ingår i: BMC Medicine. - : BioMed Central (BMC). - 1741-7015. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The identification of effective dementia prevention strategies is a major public health priority, due to the enormous and growing societal cost of this condition. Consumption of a Mediterranean diet (MedDiet) has been proposed to reduce dementia risk. However, current evidence is inconclusive and is typically derived from small cohorts with limited dementia cases. Additionally, few studies have explored the interaction between diet and genetic risk of dementia.METHODS: We used Cox proportional hazard regression models to explore the associations between MedDiet adherence, defined using two different scores (Mediterranean Diet Adherence Screener [MEDAS] continuous and Mediterranean diet Pyramid [PYRAMID] scores), and incident all-cause dementia risk in 60,298 participants from UK Biobank, followed for an average 9.1 years. The interaction between diet and polygenic risk for dementia was also tested.RESULTS: Higher MedDiet adherence was associated with lower dementia risk (MEDAS continuous: HR = 0.77, 95% CI = 0.65-0.91; PYRAMID: HR = 0.86, 95% CI = 0.73-1.02 for highest versus lowest tertiles). There was no significant interaction between MedDiet adherence defined by the MEDAS continuous and PYRAMID scores and polygenic risk for dementia.CONCLUSIONS: Higher adherence to a MedDiet was associated with lower dementia risk, independent of genetic risk, underlining the importance of diet in dementia prevention interventions.
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| 9. |
- Shannon, Oliver M., et al.
(författare)
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Mediterranean Diet Increases Endothelial Function in Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
- 2020
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Ingår i: Journal of Nutrition. - : Elsevier BV. - 1541-6100 .- 0022-3166. ; 150:5, s. 1151-1159
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Forskningsöversikt (refereegranskat)abstract
- Background: The endothelium plays a key role in the maintenance of vascular health and represents a potential physiological target for dietary and other lifestyle interventions designed to reduce the risk of cardiovascular diseases (CVD) including stroke or coronary heart disease. Objective: To conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating the effects of the Mediterranean dietary pattern (MedDiet) on endothelial function. Methods: Medline, Embase, and Scopus databases were searched from inception until January 2019 for studies that met the following criteria: 1) RCTs including adult participants, 2) interventions promoting the MedDiet, 3) inclusion of a control group, and 4) measurements of endothelial function. A random-effects meta-analysis was conducted. Metaregression and subgroup analyses were performed to identify whether effects were modified by health status (i.e., healthy participants versus participants with existing comorbidities), type of intervention (i.e., MedDiet alone or with a cointervention), study duration, study design (i.e., parallel or crossover), BMI, and age of participants. Results: Fourteen articles reporting data for 1930 participants were included in the meta-analysis. Study duration ranged from 4 wk to 2.3 y. We observed a beneficial effect of the MedDiet on endothelial function [standardized mean difference (SMD): 0.35; 95% CI: 0.17, 0.53; P <0.001; I-2 = 73.68%]. MedDiet interventions improved flow-mediated dilation (FMD)-the referencemethod for noninvasive, clinical measurement of endothelial function-by 1.66% (absolute change; 95% CI: 1.15, 2.17; P <0.001; I-2 = 0%). Effects of the MedDiet on endothelial function were not modified by health status, type of intervention, study duration, study design, BMI, or age of participants (P >0.05). Conclusions: MedDiet interventions improve endothelial function in adults, suggesting that the protective effects of the MedDiet are evident at early stages of the atherosclerotic process with important implications for the early prevention of CVD.
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