Genetics of kidney disease in diverse populations
不同人群肾脏疾病的遗传学
基本信息
- 批准号:10247520
- 负责人:
- 金额:$ 54.32万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-09-22 至 2023-07-31
- 项目状态:已结题
- 来源:
- 关键词:APOL1 geneAddressAffectAfricanAfrican AmericanAgeAlbuminsAlbuminuriaAllelesAmerican IndiansAmerindianAreaAsiansBiologicalBiological MarkersBiological ModelsBiological ProcessCandidate Disease GeneCardiovascular DiseasesCessation of lifeChronic Kidney FailureDataDevelopmentDiseaseEnd stage renal failureEpigenetic ProcessEthnic OriginEthnic groupEuropeanExcretory functionGenderGene TargetingGenesGeneticGenetic DeterminismGenetic ResearchGenetic RiskGlomerular Filtration RateHealthHigh PrevalenceHispanic AmericansHispanic Community Health Study/Study of LatinosHispanicsIn VitroIncidenceIndividualInjury to KidneyInternational Classification of Disease CodesInterventionKidneyKidney DiseasesLatinoMapsMeta-AnalysisMissionMolecularMorbidity - disease rateMusNational Institute of Diabetes and Digestive and Kidney DiseasesNatural HistoryNucleic Acid Regulatory SequencesOrthologous GeneParticipantPersonsPopulationPopulation HeterogeneityPredispositionPrognostic MarkerPublic HealthPublishingRaceRenal functionResearchRiskRisk FactorsRoleSickle CellSickle Cell TraitSodium ChlorideSouth AsianTestingTissuesTransgenic OrganismsUnderrepresented PopulationsUrineVariantVeteransadmixture mappingclinical biomarkersdifferential expressiondisease phenotypedisorder riskethnic disparityexperimental studygenetic epidemiologygenetic risk factorgenetic variantgenome wide association studygenome-widegenomic locushealth disparityhigh riskimprovedin vivoinsightkidney cellmouse modelnovelpersonalized medicineprecision medicineprematureprospectiverecruitresponserisk variantsearchable databasetherapy developmenttrait
项目摘要
ABSTRACT
Chronic kidney disease affects one in 10 people worldwide, and it contributes to premature morbidity and
death. The underlying mechanisms for its development and predisposition are unknown, limiting progress in
the identification of prognostic biomarkers or the development of treatment interventions. There are known
ethnic disparities in chronic kidney disease risk, yet little research has been done in diverse (non-European)
populations. Studies have identified several ancestral variants (e.g., APOL1, sickle cell) conferring risk of
chronic kidney disease in persons of African ancestry including admixed Hispanics/Latinos. To better
understand the genetic risk for chronic kidney disease across diverse populations, we recently established the
Continental Origins and Genetic Epidemiology Network Kidney (COGENT-Kidney) Consortium, which includes
71,638 participants from four major ancestral groups (African, Hispanic/Latino, European and East Asian).
Using novel trans-ethnic meta-analysis approaches, we identified 20 loci for kidney function and showed
important gains in uncovering functional variants within loci using diverse populations. The current proposal
seeks to provide important needed information to address the contribution of ancestry-specific variants to the
natural history of chronic kidney disease phenotypes in under-studied Hispanics/Latinos (Aim 1), by leveraging
the comprehensive longitudinal data in over 12,000 participants of the Hispanic Community Health Study/Study
of Latino. To identify novel genetic loci and underlying mechanisms that are relevant to all ancestries, we
propose to recruit additional studies to the COGENT-Kidney Consortium for an unprecedented trans-ethnic
meta-analysis of kidney traits, including a total of over 622,000 participants from diverse populations (East and
South Asian, Hispanic/Latino, African and African American, American Indian, and white) (Aim 2). We will
prioritize genes to test their functional role in in vitro experiments and mouse models of kidney injury (Aim 3).
Our results can provide important insight into genetic contributions to ethnic disparities in chronic kidney
disease risk and to inform on molecular mechanisms related to chronic kidney disease development.
Ultimately, this research could inform personalized medicine and improve the understanding and management
of kidney health and disease.
摘要
慢性肾脏疾病影响全世界十分之一的人,它导致过早发病,
死亡其发展和易感性的潜在机制尚不清楚,这限制了其进展。
预后生物标志物的鉴定或治疗干预措施的开发。存在已知
慢性肾脏疾病风险的种族差异,但在不同人群(非欧洲人)中几乎没有研究
人口。研究已经确定了几种祖先变体(例如,APOL 1,镰状细胞),
非洲血统人群(包括西班牙裔/拉丁裔混合人群)的慢性肾病。更好地
为了了解不同人群中慢性肾病的遗传风险,我们最近建立了
Continental Origins and Genetic Epidemiology Network Kidney(COGENT-Kidney)Consortium,包括
来自四个主要祖先群体(非洲人、西班牙裔/拉丁美洲人、欧洲人和东亚人)的71 638名参与者。
使用新的跨种族荟萃分析方法,我们确定了20个肾功能位点,并显示
在使用不同群体揭示基因座内的功能变体方面的重要收获。现时的建议
旨在提供重要的必要信息,以解决祖先特异性变异对
研究不足的西班牙裔/拉丁裔人群中慢性肾脏疾病表型的自然史(目标1),通过利用
西班牙裔社区健康研究/研究的12,000多名参与者的综合纵向数据
拉丁裔。为了确定与所有祖先相关的新的遗传位点和潜在机制,我们
建议为COGENT肾脏联盟招募更多研究,以进行前所未有的跨种族研究。
肾脏性状的荟萃分析,包括来自不同人群(东部和南部)的总计超过622,000名参与者。
南亚人、西班牙裔/拉丁裔、非洲人和非裔美国人、美洲印第安人和白色人)(目标2)。我们将
优先考虑基因,以测试它们在体外实验和肾损伤小鼠模型中的功能作用(目标3)。
我们的研究结果可以为慢性肾脏病的种族差异的遗传贡献提供重要的见解。
疾病风险,并告知与慢性肾脏疾病发展相关的分子机制。
最终,这项研究可以为个性化医疗提供信息,并改善对疾病的理解和管理。
肾脏健康和疾病的关系。
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)
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Nora Franceschini其他文献
Nora Franceschini的其他文献
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{{ truncateString('Nora Franceschini', 18)}}的其他基金
Mentored Training in Molecular Epidemiology of Chronic Kidney Disease in Diverse Populations
不同人群慢性肾脏病分子流行病学指导培训
- 批准号:
10799234 - 财政年份:2023
- 资助金额:
$ 54.32万 - 项目类别:
Multi-omics study of ancestry enriched associations in Hispanics/Latinos
西班牙裔/拉丁裔血统丰富关联的多组学研究
- 批准号:
10889299 - 财政年份:2023
- 资助金额:
$ 54.32万 - 项目类别:
Genetics of Cardiovascular Disease in Chronic Kidney Disease
慢性肾脏病心血管疾病的遗传学
- 批准号:
10593089 - 财政年份:2022
- 资助金额:
$ 54.32万 - 项目类别:
Genetics of Cardiovascular Disease in Chronic Kidney Disease
慢性肾脏病心血管疾病的遗传学
- 批准号:
10467373 - 财政年份:2022
- 资助金额:
$ 54.32万 - 项目类别:
Genetics of kidney disease in diverse populations
不同人群肾脏疾病的遗传学
- 批准号:
9791177 - 财政年份:2018
- 资助金额:
$ 54.32万 - 项目类别:
Genetics of kidney disease in diverse populations
不同人群肾脏疾病的遗传学
- 批准号:
10452691 - 财政年份:2018
- 资助金额:
$ 54.32万 - 项目类别:
APOL1, sickle cell trait and chronic kidney disease in African Americans
APOL1、镰状细胞特征和非裔美国人的慢性肾病
- 批准号:
9337929 - 财政年份:2016
- 资助金额:
$ 54.32万 - 项目类别:
Trans-ethnic meta-analysis of blood pressure in African and European ancestries
非洲和欧洲血统血压的跨种族荟萃分析
- 批准号:
8755381 - 财政年份:2014
- 资助金额:
$ 54.32万 - 项目类别:
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