Genetic analysis of the Dutch Hunger Winter Families Study to Boost Rigor and Robustness for Testing In-Utero Famine Effects on Aging-Related Health Conditions and Biological Aging
荷兰饥饿冬季家庭研究的遗传分析,以提高测试宫内饥荒对衰老相关健康状况和生物衰老影响的严谨性和稳健性
基本信息
- 批准号:10626012
- 负责人:
- 金额:$ 51.51万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-05-15 至 2025-04-30
- 项目状态:未结题
- 来源:
- 关键词:AccelerationAccountingAddressAdultAffectAgeAgingAnimal ExperimentsBiologicalBiological AgingBiological AssayBirthBirth RateBloodBlood specimenCardiometabolic DiseaseCharacteristicsChildChronic DiseaseClinicalCognitiveConceptionsDNA MethylationDNA SequenceDataDatabasesDevelopmentDiseaseElderlyEpigenetic ProcessEventExposure toFamily StudyFaminesFertilityFetal Growth RetardationFetal Mortality StatisticsFutureGeneticGenetic VariationGenomicsGenotypeGoalsHealthHumanHungerIndividualInfantInterventionKnowledgeLifeLife Cycle StagesLinkLong-Term EffectsLongevityMeasuresMediatorMethylationModelingNatural experimentNon-Insulin-Dependent Diabetes MellitusObesityObservational StudyOnset of illnessOutcomeParticipantPathologyPathway interactionsPerinatalPopulationPrevention strategyProcessPublishingQuantitative Trait LociResearchResourcesRiskSampling StudiesSelection BiasSiblingsSurvivorsTestingTimeWarWorkage relatedcardiometabolismcognitive reservecognitive testingcohortevidence baseexperimental studyfetalfollow-upgenetic analysisgenetic approachgenetic informationgenetic selectiongenetic testinggenetic variantgenome wide association studygenome-widehealthspanimprovedin uteroknowledge basemembermultiple omicsnovel strategiesperinatal periodpolygenic risk scoreprenatalpreventpublic health prioritiesrandomized trialstudy populationtreatment strategyunethicalwhole genome
项目摘要
SUMMARY
The graying global population makes interventions to extend healthy lifespan a public heath priority. Health
insults during the perinatal period are linked with risk for aging-related health conditions, including obesity, type
2 diabetes, and cardio-metabolic disease. If these associations are causal, interventions to prevent perinatal
insults and to reverse their biological damage could delay disease onset and prolong healthspan. However,
establishing causal long-term health effects of perinatal insults in humans is challenging. Randomized trials
would be unethical. Observational studies can be biased by confounding factors that erroneously suggest a
link between insults in the perinatal period and later health. In contrast, natural experiments can isolate the
impact of perinatal insults on adult disease and healthspan. The Dutch Hunger Winter Families Study
(DHWFS) uses a sudden, war-induced famine as a natural experiment. The famine was caused by a Nazi
blockade during WWII in 1944-45. Because the impact of famine was immediate, transient, and population-
wide, DHWFS comparison of infants born during the famine with those born before or after the famine will
identify potential long-term effects of perinatal-insults. However, famine natural-experiment studies, including
DHWFS, may be vulnerable to selection bias. Birth rates decline significantly during famine; famine’s impact on
fertility and fetal/infant survival might bias famine studies of perinatal insult’s long-term effects in unknown
ways. To fill this gap in knowledge, we will genotype stored DHWFS biospecimens from of N=956 individuals,
37% of whom were exposed to famine in-utero and the remainder of whom are siblings of the famine-exposed
individuals and “time controls” born immediately before or after the famine. We will link new genetic data with
participants’ existing clinical and cognitive tests and blood DNA methylation data. We will examine in this
integrative multi-omics database the potential impact of selective fertility and fetal/infant survival during the
famine on (i) genome wide genetic characteristics; (ii) differences in polygenic risk scores for specific aging-
related health conditions; and (iii) differences in methylation quantitative trait loci (mQTL) genotypes. We will
then conduct genetics-informed analysis of famine effects on obesity, type-2 diabetes, cognitive reserve, and
epigenetic aging. Using these new resources, we will prepare an integrated multi-omics database of the
DHWFS population for use by outside research teams and generate a one of a kind resource for famine and
perinatal insult research. The proposed project will generate a new knowledge base to further examine
biological pathways that are likely to connect perinatal events to adult health and aging through genetic and
epigenetic mechanisms.
总结
全球人口老龄化使延长健康寿命的干预措施成为公共卫生的优先事项。健康
在围产期的侮辱与年龄相关的健康状况,包括肥胖,类型,
2糖尿病和心脏代谢疾病。如果这些关联是因果关系,
因此,通过减少和消除这些疾病的生物学损害,可以延缓疾病的发作,延长健康寿命。然而,在这方面,
确定围产期损伤对人类健康的长期因果影响具有挑战性。随机试验
是不道德的观察性研究可能会受到混淆因素的影响,这些因素错误地表明,
围产期的伤害与以后的健康之间的联系。相比之下,自然实验可以分离出
围产期损伤对成人疾病和健康寿命影响。荷兰饥饿冬季家庭研究
(DHWFS)使用一个突然的,战争引起的饥荒作为一个自然实验。饥荒是由一个纳粹分子引起的
1944- 1945年二战期间的封锁。因为饥荒的影响是直接的,短暂的,人口-
卫生福利和家庭服务部将饥荒期间出生的婴儿与饥荒之前或之后出生的婴儿进行比较,
确定围产期损伤的潜在长期影响。然而,饥荒自然实验研究,包括
DHWFS可能易受选择偏差的影响。饥荒期间出生率显著下降;饥荒对
生育率和胎儿/婴儿存活率可能会使关于围产期损伤的长期影响的饥荒研究产生偏差,
的方式为了填补这一知识空白,我们将对N=956名个体中存储的DHWFS生物标本进行基因分型,
其中37%的人在子宫内遭受饥荒,其余的人是饥荒暴露的兄弟姐妹。
在饥荒之前或之后出生的个人和“时间控制”。我们将把新的基因数据与
参与者现有的临床和认知测试以及血液DNA甲基化数据。我们将在这方面进行研究,
综合性多组学数据库:选择性生育和胎儿/婴儿存活的潜在影响
饥荒(i)全基因组遗传特征;(ii)特定衰老的多基因风险评分差异-
相关的健康状况;和(iii)甲基化数量性状基因座(mQTL)基因型的差异。我们将
然后进行遗传学分析饥荒对肥胖,2型糖尿病,认知储备的影响,
表观遗传老化利用这些新的资源,我们将准备一个综合的多组学数据库,
DHWFS人口供外部研究小组使用,并产生一种用于饥荒的资源,
围产期损伤研究。拟议的项目将产生一个新的知识库,
生物学途径,可能通过遗传和遗传途径将围产期事件与成人健康和衰老联系起来,
表观遗传机制
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Daniel Walker Belsky其他文献
Daniel Walker Belsky的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Daniel Walker Belsky', 18)}}的其他基金
The MyGoals for Healthy Aging Multi-Center Randomized Controlled Trial
MyGoals 健康老龄化多中心随机对照试验
- 批准号:
10677637 - 财政年份:2022
- 资助金额:
$ 51.51万 - 项目类别:
The MyGoals for Healthy Aging Multi-Center Randomized Controlled Trial
MyGoals 健康老龄化多中心随机对照试验
- 批准号:
10800917 - 财政年份:2022
- 资助金额:
$ 51.51万 - 项目类别:
The MyGoals for Healthy Aging Multi-Center Randomized Controlled Trial
MyGoals 健康老龄化多中心随机对照试验
- 批准号:
10446592 - 财政年份:2022
- 资助金额:
$ 51.51万 - 项目类别:
Genetic analysis of the Dutch Hunger Winter Families Study to Boost Rigor and Robustness for Testing In-Utero Famine Effects on Aging-Related Health Conditions and Biological Aging
荷兰饥饿冬季家庭研究的遗传分析,以提高测试宫内饥荒对衰老相关健康状况和生物衰老影响的严谨性和稳健性
- 批准号:
10831121 - 财政年份:2020
- 资助金额:
$ 51.51万 - 项目类别:
Development of a DNA methylation data resource for exposome research on Alzheiemer's Disease and Related Dementias within the Dutch Hunger Winter Families Study
荷兰饥饿冬季家庭研究中开发用于阿尔茨海默病和相关痴呆症暴露组研究的 DNA 甲基化数据资源
- 批准号:
10661283 - 财政年份:2020
- 资助金额:
$ 51.51万 - 项目类别:
Genetic analysis of the Dutch Hunger Winter Families Study to Boost Rigor and Robustness for Testing In-Utero Famine Effects on Aging-Related Health Conditions and Biological Aging
荷兰饥饿冬季家庭研究的遗传分析,以提高测试宫内饥荒对衰老相关健康状况和生物衰老影响的严谨性和稳健性
- 批准号:
10159838 - 财政年份:2020
- 资助金额:
$ 51.51万 - 项目类别:
Genetic analysis of the Dutch Hunger Winter Families Study to Boost Rigor and Robustness for Testing In-Utero Famine Effects on Aging-Related Health Conditions and Biological Aging
荷兰饥饿冬季家庭研究的遗传分析,以提高测试宫内饥荒对衰老相关健康状况和生物衰老影响的严谨性和稳健性
- 批准号:
10410379 - 财政年份:2020
- 资助金额:
$ 51.51万 - 项目类别:
Genomic Analysis of the CALERIE Trial to Generate New Knowledge for Geroscience
CALERIE 试验的基因组分析,为老年科学产生新知识
- 批准号:
10378000 - 财政年份:2019
- 资助金额:
$ 51.51万 - 项目类别:
Genomic Analysis of the CALERIE Trial to Generate New Knowledge for Geroscience
CALERIE 试验的基因组分析,为老年科学产生新知识
- 批准号:
9973115 - 财政年份:2019
- 资助金额:
$ 51.51万 - 项目类别:
Genomic Analysis of the CALERIE Trial to Generate New Knowledge for Geroscience
CALERIE 试验的基因组分析,为老年科学产生新知识
- 批准号:
10612785 - 财政年份:2019
- 资助金额:
$ 51.51万 - 项目类别:
相似海外基金
Unraveling the Dynamics of International Accounting: Exploring the Impact of IFRS Adoption on Firms' Financial Reporting and Business Strategies
揭示国际会计的动态:探索采用 IFRS 对公司财务报告和业务战略的影响
- 批准号:
24K16488 - 财政年份:2024
- 资助金额:
$ 51.51万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Mighty Accounting - Accountancy Automation for 1-person limited companies.
Mighty Accounting - 1 人有限公司的会计自动化。
- 批准号:
10100360 - 财政年份:2024
- 资助金额:
$ 51.51万 - 项目类别:
Collaborative R&D
Accounting for the Fall of Silver? Western exchange banking practice, 1870-1910
白银下跌的原因是什么?
- 批准号:
24K04974 - 财政年份:2024
- 资助金额:
$ 51.51万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
A New Direction in Accounting Education for IT Human Resources
IT人力资源会计教育的新方向
- 批准号:
23K01686 - 财政年份:2023
- 资助金额:
$ 51.51万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
An empirical and theoretical study of the double-accounting system in 19th-century American and British public utility companies
19世纪美国和英国公用事业公司双重会计制度的实证和理论研究
- 批准号:
23K01692 - 财政年份:2023
- 资助金额:
$ 51.51万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
An Empirical Analysis of the Value Effect: An Accounting Viewpoint
价值效应的实证分析:会计观点
- 批准号:
23K01695 - 财政年份:2023
- 资助金额:
$ 51.51万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Accounting model for improving performance on the health and productivity management
提高健康和生产力管理绩效的会计模型
- 批准号:
23K01713 - 财政年份:2023
- 资助金额:
$ 51.51万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
CPS: Medium: Making Every Drop Count: Accounting for Spatiotemporal Variability of Water Needs for Proactive Scheduling of Variable Rate Irrigation Systems
CPS:中:让每一滴水都发挥作用:考虑用水需求的时空变化,主动调度可变速率灌溉系统
- 批准号:
2312319 - 财政年份:2023
- 资助金额:
$ 51.51万 - 项目类别:
Standard Grant
New Role of Not-for-Profit Entities and Their Accounting Standards to Be Unified
非营利实体的新角色及其会计准则将统一
- 批准号:
23K01715 - 财政年份:2023
- 资助金额:
$ 51.51万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Improving Age- and Cause-Specific Under-Five Mortality Rates (ACSU5MR) by Systematically Accounting Measurement Errors to Inform Child Survival Decision Making in Low Income Countries
通过系统地核算测量误差来改善特定年龄和特定原因的五岁以下死亡率 (ACSU5MR),为低收入国家的儿童生存决策提供信息
- 批准号:
10585388 - 财政年份:2023
- 资助金额:
$ 51.51万 - 项目类别: