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Using Genetic and Blood Metabolites to Understand the Risk of Alzheimer's Disease in Latinos

利用遗传和血液代谢物了解拉丁裔患阿尔茨海默病的风险

基本信息

批准号：
10299916
负责人：
Tamar Sofer
金额：
$ 45.56万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-30 至 2023-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10299916
关键词：
Accounting Adult Affect Aging Alleles Alzheimer&apos s Disease Alzheimer&apos s disease model Alzheimer&apos s disease related dementia Alzheimer&apos s disease risk Alzheimer’s disease biomarker Amerindian Ancillary Study Applications Grants Awareness Biological Markers Blood Brain Caribbean region Central America Cognitive Cuban Data Data Collection Data Set Dementia Development Disease Early Diagnosis Elderly Environment Equation Ethnic group Etiology Future Genes Genetic Genetic Determinism Genetic Heterogeneity Genetic study Genome Genomic Segment Glean Goals Heterogeneity High Prevalence Hispanic Community Health Study/Study of Latinos Hispanics Impaired cognition Individual Informatics Inherited Joints Latino Lead Life Style Literature Magnetic Resonance Imaging Manuscripts Measures Mexican Minority Groups Modeling Native Americans Neurocognitive Neurocognitive Deficit Not Hispanic or Latino Other Genetics Pathway interactions Phenotype Population Population Heterogeneity Process Publishing Puerto Rican Race Recommendation Research Role South America Stratification Structure Study models Subgroup Testing Variant Visit Work admixture mapping base cognitive change cognitive function design early detection biomarkers follow-up genome wide association study health disparity human disease indexing interest lifestyle factors machine learning algorithm metabolome metabolomics middle age mild cognitive impairment polygenic risk score potential biomarker predictive modeling programs racial and ethnic risk prediction socioeconomic disadvantage trait

项目摘要

U.S. Latinos are highly diverse, with individuals originating from central and south America, as well as the Caribbean. Latinos are socioeconomically disadvantaged compared to U.S. Whites, and suffer from a higher prevalence of Alzheimer’s disease and related dementia. Genetic determinants of Alzheimer’s disease may be somewhat different in Latinos compared to Whites: in preliminary results, we found that genetic background, in the form of proportion of genome inherited from Amerindian (Native American) ancestors mitigates the detrimental effect of the APOE-𝜖𝜖4 variants on cognitive decline in individuals from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). This suggests heterogeneity in genetically-based mechanisms underlying neurocognitive decline in Latinos. Untargeted metabolomics is a promising approach to develop potential biomarkers for human disease. Previous metabolomics studies identified potential biomarkers for Alzheimer’s disease and for cognitive traits in a cross- sectional manner, however, very little work was done specifically in Latinos, and the genetics and metabolomics have not been integrated for risk prediction, apart from using APOE-𝜖𝜖4. Here, we propose to utilize a dataset including ~1,500 older Latino adults from the HCHS/SOL with untargeted metabolomics measured at a baseline visit, and neurocognitive function estimated in both the baseline and a follow-up visit. Our goals are: (1) develop preliminary biomarkers for aging-related cognitive decline phenotypes (e.g. change in global cognitive function, mild cognitive impairment); (2) study the genetic basis of the association of metabolites with cognitive decline, and study potential heterogeneity by genetic background; and (3) form recommendations and a grant application to support a larger research program utilizing genetics and metabolomics, and potentially other ‘omics, to develop biomarkers of Alzheimer’s disease in diverse populations, and study underlying mechanisms.

美国的拉丁美洲人非常多样化，有来自中美洲和南美洲的人，也有来自拉丁美洲的人