Linking microbiome genetic variants with cardiovascular phenotypes in 50,000 individuals
将 50,000 名个体的微生物组遗传变异与心血管表型联系起来
基本信息
- 批准号:10516693
- 负责人:
- 金额:$ 70.73万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-08-01 至 2026-05-31
- 项目状态:未结题
- 来源:
- 关键词:AccountingAddressAlgorithmsAllelesAnimal ModelAtherosclerosisBacterial GenesBenchmarkingBiological MarkersBiologyCardiovascular Diagnostic TechniquesCardiovascular DiseasesCardiovascular systemCellsCodeCommunitiesComplexComplex MixturesCopy Number PolymorphismCountryDNADataData SetDevelopmentDietDiseaseDrug TargetingEnsureGene DosageGene FamilyGene FrequencyGenesGeneticGenetic RecombinationGenetic VariationGenomeGenotypeGoalsHaploidyHealthHeart DiseasesHomeHumanHuman GeneticsHuman MicrobiomeHuman bodyIn SituIndividualInflammationInvestigationIsraelLabelLevocarnitineLife StyleLinear ModelsLinkMeasurementMeasuresMediatingMedical RecordsMetabolicMetagenomicsMethodsMicrobeModelingOutcomePan GenusPathway interactionsPatternPersonsPharmaceutical PreparationsPhenotypePhylogenetic AnalysisPhysiologyPopulationPopulation GeneticsPreventionProbioticsProcessResearchResolutionRunningSamplingShotgun SequencingShotgunsSingle Nucleotide PolymorphismStatistical ModelsStructureTaxonomyTestingUnited StatesUnmarried personVariantacute coronary syndromebasebioinformatics toolcardiovascular disorder riskcohortcomputational platformcostdesigndrug metabolismgenetic approachgenetic variantgut microbesgut microbiomeheart functionhost-microbe interactionsinsightmetabolomicsmetagenomemetagenomic sequencingmicrobialmicrobiomemicroorganismnovelopen sourcepersonalized medicinepopulation genetic structureprebioticsprecision medicinesimulationtherapeutic targettooltrait
项目摘要
PROJECT SUMMARY / ABSTRACT
The human body is home to a complex community of microorganisms (“microbiome”) that differs in composition
between people, with numerous correlates to cardiovascular disease (CVD). Any two people will harbor different
strains of a given species, which can be more genetically different than a human and chimpanzee with <60% of
their genes shared. Even within a single person, each microbiome species may be a complex mixture of strains
with different genomes and functional capabilities. This striking within-species genetic diversity has functional
consequences for CVD, because gene loss and gain modify how strains process our diet, metabolize drugs, and
stimulate inflammation. Hence, a population genetic approach is essential for revealing causal links between the
microbiome and CVD.
We have compiled a deeply phenotyped cohort of ~50,000 individuals with metagenomic sequencing of their gut
microbiomes. This dataset includes ~8,000 people with atherosclerosis, thousands with measurements of heart
function and metabolic health, and hundreds with acute coronary syndrome. This cohort is a unique and ideal
setting to perform a well-powered CVD metagenome-wide association study (MWAS).
Several barriers must be overcome before MWAS can be deployed at this scale. First, we must reduce the
infeasible computational cost of genotyping thousands of microbiome species across ~50,000 people. Second,
to ensure that statistical tests for associations do not have high false positive rates we need statistical models
that adjust for microbial population structure within and across hosts. The goal of this proposal is to create a
research toolbox to address these challenges as well as to identify putative mechanistic links between
microbiome and CVD. We will develop data structures and query algorithms for accelerated genotype estimation
and mixed effects models for accurate association tests. All code and methods will be open source and designed
to be easily extended to other microbiome cohorts.
Applying these tools to our cohort, we aim to identify specific microbial genes and pathways responsible for
known associations between microbes and CVD. We also expect to discover new associations that were missed
because cohorts were too small or they were analyzed with methods that ignore differences in gene content
across strains. These findings will be used to identify microbial biomarkers for CVD diagnosis and personalized
treatments or to design microbiome targeted drugs, prebiotics, and probiotics to treat heart disease.
项目摘要/摘要
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 }}
KATHERINE S. POLLARD其他文献
KATHERINE S. POLLARD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('KATHERINE S. POLLARD', 18)}}的其他基金
Discovering human divergent activity-regulated elements using comparative, computational, and functional approaches
使用比较、计算和功能方法发现人类不同活动调节的元素
- 批准号:
10779701 - 财政年份:2023
- 资助金额:
$ 70.73万 - 项目类别:
Linking microbiome genetic variants with cardiovascular phenotypes in 50,000 individuals
将 50,000 名个体的微生物组遗传变异与心血管表型联系起来
- 批准号:
10672312 - 财政年份:2022
- 资助金额:
$ 70.73万 - 项目类别:
Resolving single-cell brain regulatory elements with bulk data supervised models
用批量数据监督模型解决单细胞大脑调节元件
- 批准号:
10362579 - 财政年份:2020
- 资助金额:
$ 70.73万 - 项目类别:
Resolving single-cell brain regulatory elements with bulk data supervised models
用批量数据监督模型解决单细胞大脑调节元件
- 批准号:
10579845 - 财政年份:2020
- 资助金额:
$ 70.73万 - 项目类别:
Resolving single-cell brain regulatory elements with bulk data supervised models
用批量数据监督模型解决单细胞大脑调节元件
- 批准号:
10007660 - 财政年份:2020
- 资助金额:
$ 70.73万 - 项目类别:
相似海外基金
Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
- 批准号:
MR/S03398X/2 - 财政年份:2024
- 资助金额:
$ 70.73万 - 项目类别:
Fellowship
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
- 批准号:
2338423 - 财政年份:2024
- 资助金额:
$ 70.73万 - 项目类别:
Continuing Grant
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
- 批准号:
EP/Y001486/1 - 财政年份:2024
- 资助金额:
$ 70.73万 - 项目类别:
Research Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
- 批准号:
MR/X03657X/1 - 财政年份:2024
- 资助金额:
$ 70.73万 - 项目类别:
Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
- 批准号:
2348066 - 财政年份:2024
- 资助金额:
$ 70.73万 - 项目类别:
Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
- 批准号:
AH/Z505481/1 - 财政年份:2024
- 资助金额:
$ 70.73万 - 项目类别:
Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10107647 - 财政年份:2024
- 资助金额:
$ 70.73万 - 项目类别:
EU-Funded
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
- 批准号:
2341402 - 财政年份:2024
- 资助金额:
$ 70.73万 - 项目类别:
Standard Grant
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10106221 - 财政年份:2024
- 资助金额:
$ 70.73万 - 项目类别:
EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
- 批准号:
AH/Z505341/1 - 财政年份:2024
- 资助金额:
$ 70.73万 - 项目类别:
Research Grant