HDHL DIMENSION: Dietary induced methylome and transcriptome dynamics assessing nutrition impacts on cardiovascular and metabolic health
HDHL 维度:饮食诱导的甲基化组和转录组动态评估营养对心血管和代谢健康的影响
基本信息
- 批准号:BB/S020845/1
- 负责人:
- 金额:$ 34.12万
- 依托单位:
- 依托单位国家:英国
- 项目类别:Research Grant
- 财政年份:2019
- 资助国家:英国
- 起止时间:2019 至 无数据
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Cardiovascular and metabolic diseases are a primary cause of morbidity and mortality worldwide. Diet is a major risk factor for cardio-metabolic health, but is challenging to study in part because metabolic response to diet is highly individualised. Characterising the molecular pathways that mediate personalised responses to diet is critical to effectively tackle the current epidemic. Epigenetic mechanisms are key regulators of gene function that can change in response to external stimuli, including diet. However, longitudinal studies of epigenetic dynamics in response to diet are rare. Our hypothesis is that the identification of dietary induced epigenetic marks together with epigenetic signatures of cardio-metabolic traits explain inter-individual variability in metabolic response to diet and its downstream effects on health. The DIMENSION consortium will test this hypothesis by investigating dynamically the causal impacts of dietary intake on epigenetic regulation of gene function across tissues, and their impact on subsequent cardio-metabolic health outcomes. The proposal will explore the gene regulatory and functional pathways that occur immediately following food intake in the postprandial state, as well as with habitual dietary intakes. We will test postprandial metabolic responses that have been largely overlooked, despite revealing multiple aspects of diet induced metabolic health that would not be detectable from studying fasting status alone. Further, humans spend the majority of their lives in the postprandial glycemic and lipemic state, which are themselves independent risk factors of cardiovascular disease. The work programme is based on: (i) targeted postprandial and nutritional intervention studies to tackle the causal relationships between diet, epigenetic modifications and gene function, in combination with (ii) state-of-the-art analyses to characterize the links between diet, epigenetics, and cardio-metabolic health using novel diet measures including metabolomics in extensively studied cohorts, and (iii) functional follow-up experiments assessing the impact of diet-induced epigenetic and transcriptomic signals at the level of cells, within and across tissues. Using complementary approaches, the DIMENSION consortium will deliver novel mechanistic insights into how exactly nutritional modifications can modulate the regulatory and functional genome to promote cardio-metabolic health. These insights will complement traditional population-based guidelines and inform the rapidly evolving area of individualised nutrition-based strategies.
心血管和代谢疾病是全球发病和死亡的主要原因。饮食是心脏代谢健康的主要风险因素,但部分研究具有挑战性,因为对饮食的代谢反应是高度个性化的。表征介导对饮食的个性化反应的分子途径对于有效应对当前的流行病至关重要。表观遗传机制是基因功能的关键调节器,可以响应于外部刺激(包括饮食)而改变。然而,纵向研究的表观遗传动态饮食反应是罕见的。我们的假设是,饮食诱导的表观遗传标记的识别与心脏代谢性状的表观遗传特征一起解释了对饮食的代谢反应及其对健康的下游影响的个体间差异。DIMENSION联盟将通过动态调查饮食摄入对各组织基因功能表观遗传调控的因果影响及其对后续心脏代谢健康结果的影响来验证这一假设。该提案将探索在餐后状态下食物摄入后立即发生的基因调控和功能途径,以及习惯性饮食摄入。我们将测试餐后代谢反应,这些反应在很大程度上被忽视了,尽管揭示了饮食诱导的代谢健康的多个方面,而这些方面仅通过研究空腹状态是无法检测到的。此外,人类一生的大部分时间都处于餐后血糖和血脂状态,这本身就是心血管疾病的独立危险因素。工作方案的依据是:(i)有针对性的餐后和营养干预研究,以解决饮食,表观遗传修饰和基因功能之间的因果关系,结合(ii)最先进的分析,以表征饮食,表观遗传学和心脏代谢健康之间的联系,使用新的饮食措施,包括广泛研究的队列中的代谢组学,和(iii)功能性随访实验,评估饮食诱导的表观遗传和转录组信号在细胞水平、组织内和组织间的影响。使用互补的方法,DIMENSION联盟将提供新的机制见解,了解营养修饰如何准确地调节调节和功能基因组,以促进心脏代谢健康。这些见解将补充传统的基于人群的指南,并为快速发展的个性化营养策略领域提供信息。
项目成果
期刊论文数量(10)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Trans-ancestry epigenome-wide association meta-analysis of DNA methylation with lifetime cannabis use
- DOI:10.1038/s41380-023-02310-w
- 发表时间:2023-11-07
- 期刊:
- 影响因子:11
- 作者:Fang,Fang;Quach,Bryan;Johnson,Eric O.
- 通讯作者:Johnson,Eric O.
DNA methylation analysis is used to identify novel genetic loci associated with circulating fibrinogen levels in blood
DNA 甲基化分析用于识别与血液中循环纤维蛋白原水平相关的新遗传位点
- DOI:10.1016/j.jtha.2023.01.015
- 发表时间:2023
- 期刊:
- 影响因子:10.4
- 作者:Hahn J
- 通讯作者:Hahn J
TMAO Upregulates Members of the miR-17/92 Cluster and Impacts Targets Associated with Atherosclerosis.
TMAO上调miR-17/92簇的成员,并影响与动脉粥样硬化有关的靶标。
- DOI:10.3390/ijms232012107
- 发表时间:2022-10-11
- 期刊:
- 影响因子:5.6
- 作者:
- 通讯作者:
One-year longitudinal association between changes in dietary choline or betaine intake and cardiometabolic variables in the PREvención con DIeta MEDiterránea-Plus (PREDIMED-Plus) trial.
- DOI:10.1093/ajcn/nqac255
- 发表时间:2022-12-19
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Adipose methylome integrative-omic analyses reveal genetic and dietary metabolic health drivers and insulin resistance classifiers.
- DOI:10.1186/s13073-022-01077-z
- 发表时间:2022-07-18
- 期刊:
- 影响因子:12.3
- 作者:Christiansen C;Tomlinson M;Eliot M;Nilsson E;Costeira R;Xia Y;Villicaña S;Mompeo O;Wells P;Castillo-Fernandez J;Potier L;Vohl MC;Tchernof A;Moustafa JE;Menni C;Steves CJ;Kelsey K;Ling C;Grundberg E;Small KS;Bell JT
- 通讯作者:Bell JT
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Jordana Bell其他文献
Jordana Bell的其他文献
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{{ truncateString('Jordana Bell', 18)}}的其他基金
BACMETH: Bacterial methylation of the human gut microbiome in response to diet for improvement of cardiometabolic health
BACMETH:人类肠道微生物组的细菌甲基化响应饮食以改善心脏代谢健康
- 批准号:
EP/Y023765/1 - 财政年份:2024
- 资助金额:
$ 34.12万 - 项目类别:
Research Grant
Taiwan Partnering Award: Artificial intelligence applications to identify regulatory genomic signatures of diet and lifestyle disease risk factors
台湾合作奖:人工智能应用识别饮食和生活方式疾病风险因素的监管基因组特征
- 批准号:
BB/T019980/1 - 财政年份:2021
- 资助金额:
$ 34.12万 - 项目类别:
Research Grant
Epigenetic responses to social and environmental cues in early life and over the life course: impact on healthy ageing in UK population-based cohorts
生命早期和整个生命过程中对社会和环境线索的表观遗传反应:对英国人口群体健康老龄化的影响
- 批准号:
ES/N000404/1 - 财政年份:2015
- 资助金额:
$ 34.12万 - 项目类别:
Research Grant
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