Role of Genetic Susceptibility in the Central American Kidney Disease Epidemic
遗传易感性在中美洲肾脏病流行中的作用
基本信息
- 批准号:9986057
- 负责人:
- 金额:$ 7.29万
- 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:2018-09-14 至 2023-06-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAffectAgricultural WorkersAgricultureAnti-inflammatoryAntibioticsAreaBiologyCanesCase-Control StudiesCentral AmericaCentral AmericanChronic Kidney FailureClinicalCommunicable DiseasesCommunitiesCosta RicaCountryDNADataDependenceDiabetes MellitusDiseaseDisease ClusteringsEl SalvadorEnrollmentEnvironmental ExposureEnvironmental Risk FactorEpidemicExertionExtended FamilyFamilyFrequenciesGenesGeneticGenetic Predisposition to DiseaseGenetic RiskGenetic studyGenotypeGoalsGovernmentGuatemalaHeat Stress DisordersHeavy MetalsHispanic AmericansHispanicsHondurasHypertensionIndividualIndustryInfectious AgentKidneyKidney DiseasesLongitudinal cohortMapsMesoamericanMexicoMiningNative AmericansNephrologyNicaraguaOccupationsParticipantPenetrancePesticidesPhysiciansPopulationPredispositionProcessPublic HealthResearchResearch DesignRiskRisk FactorsRoleSaccharumStressSuggestionSusceptibility GeneTestingUnited StatesUrineValidationVariantWaterWorkagricultural communityagricultural regionbaseburden of illnesscase controlcausal variantcohortdesigndisorder riskexome sequencingfamily structuregenetic analysisgenetic approachgenetic epidemiologygenetic risk factorgenetic variantgenome wide association studygenome-widehot climatekindredmembernephrotoxicityprospectiverecruitrisk variantstatisticssugarvalidation studiesyoung man
项目摘要
PROJECT SUMMARY
Extraordinarily high rates of chronic kidney disease have been observed on the Pacific coast of
several Central American countries including Nicaragua, El Salvador, Honduras, Guatemala,
Costa Rica, and Southern Mexico. This increasingly recognized epidemic of kidney disease,
known as Mesoamerican Nephropathy (MeN), is not associated with traditional risk factors
such as diabetes or hypertension, and affects predominately young men who work in
agriculture. Environmental factors such as heat stress, pesticides, infectious diseases, and
many others have been proposed as potential explanations, but no clear cause has emerged.
The postulated risk factors do not appear to be unique to the affected region, and they do not
explain why some agricultural workers get kidney disease while others do not. We propose
that genetic susceptibility is a major contributor to MeN risk, a hypothesis that we have
strengthened by documenting striking familial clustering of disease. We have built strong
relationships with local physicians, workers' groups, industry, and government in a MeN
hotspot in Nicaragua. We have also built an interdisciplinary team with expertise in nephrology,
genetics, epidemiology, and statistics. We have successfully enrolled nearly 1400 participants
in our studies and performed preliminary genetic analyses that strongly support a significant
genetic susceptibility to MeN, including identification of one set of genetic variants associated
with MeN at genome-wide significance levels. We propose to 1) conduct a case-control
genome-wide association study of former sugar cane workers with MeN and current healthy
workers, 2) study 40 large, multigenerational MeN kindreds using a family-based genetic
approach, and 3) validate our findings and conduct additional SNP discovery in a longitudinal
community-based cohort, as well as in miners and brick makers who are also affected by MeN.
Our study design is optimized to identify genetic risk variants with different combinations of
frequency, effect size, and dependence on environmental interactions. This project will
illuminate genetic risk factors that cause susceptibility to kidney disease in people of mixed
ancestry in our Central American neighbors and may also help us understand mechanisms
that contribute to high rates of kidney disease in other populations with Native American or
Hispanic ancestry.
项目总结
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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DANIEL R BROOKS其他文献
DANIEL R BROOKS的其他文献
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{{ truncateString('DANIEL R BROOKS', 18)}}的其他基金
Chronic Kidney Diseases of Uncertain Etiology (CKDu) in Agricultural Communities (CURE) Research Consortium - SDCC
农业社区病因不明的慢性肾脏病 (CKDu) (CURE) 研究联盟 - SDCC
- 批准号:
10300125 - 财政年份:2021
- 资助金额:
$ 7.29万 - 项目类别:
Chronic Kidney Diseases of Uncertain Etiology (CKDu) in Agricultural Communities (CURE) Research Consortium - SDCC
农业社区病因不明的慢性肾脏病 (CKDu) (CURE) 研究联盟 - SDCC
- 批准号:
10472609 - 财政年份:2021
- 资助金额:
$ 7.29万 - 项目类别:
Chronic Kidney Diseases of Uncertain Etiology (CKDu) in Agricultural Communities (CURE) Research Consortium - SDCC
农业社区病因不明的慢性肾脏病 (CKDu) (CURE) 研究联盟 - SDCC
- 批准号:
10899060 - 财政年份:2021
- 资助金额:
$ 7.29万 - 项目类别:
Chronic Kidney Diseases of Uncertain Etiology (CKDu) in Agricultural Communities (CURE) Research Consortium - SDCC
农业社区病因不明的慢性肾脏病 (CKDu) (CURE) 研究联盟 - SDCC
- 批准号:
10660991 - 财政年份:2021
- 资助金额:
$ 7.29万 - 项目类别:
Third International Workshop on Mesoamerican Nephropathy and Other CKDu
第三届中美洲肾病和其他 CKDu 国际研讨会
- 批准号:
9763189 - 财政年份:2019
- 资助金额:
$ 7.29万 - 项目类别:
Role of Genetic Susceptibility in the Central American Kidney Disease Epidemic
遗传易感性在中美洲肾脏病流行中的作用
- 批准号:
10212372 - 财政年份:2018
- 资助金额:
$ 7.29万 - 项目类别:
Role of Genetic Susceptibility in the Central American Kidney Disease Epidemic
遗传易感性在中美洲肾脏病流行中的作用
- 批准号:
9978780 - 财政年份:2018
- 资助金额:
$ 7.29万 - 项目类别:
Role of Genetic Susceptibility in the Central American Kidney Disease Epidemic
遗传易感性在中美洲肾脏病流行中的作用
- 批准号:
10445259 - 财政年份:2018
- 资助金额:
$ 7.29万 - 项目类别:
A GEOHealth hub for agriiculture and informal work in Nicaragua: - USA
尼加拉瓜农业和非正式工作 GEOHealth 中心: - 美国
- 批准号:
8549876 - 财政年份:2012
- 资助金额:
$ 7.29万 - 项目类别:
A GEOHealth Hub for Agriculture and Informal Work in Nicaragua: - USA
尼加拉瓜农业和非正式工作 GEOHealth 中心:- 美国
- 批准号:
8864871 - 财政年份:2012
- 资助金额:
$ 7.29万 - 项目类别:
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