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Whole genome sequencing of the Mexican Health Aging Study (MHAS) cohort

墨西哥健康老龄化研究 (MHAS) 队列的全基因组测序

基本信息

批准号：
10228341
负责人：
Sandra Barral Rodriguez
金额：
$ 163.61万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
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：
2020-09-15 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10228341
关键词：
African American Age-Years Aging Alzheimer&apos s Disease Alzheimer&apos s disease diagnosis Alzheimer&apos s disease risk American Biological Blood specimen Cells Clinical Clinical assessments Cognitive Cohort Studies Collection Communities Complex Country DNA Data Dementia Developed Countries Diagnostic Ensure Ethnic Origin Europe European Evaluation Functional disorder Funding Genes Genetic Genetic study Genome Genomics Genotype Goals Grant Health High Prevalence Hispanics Impaired cognition In Vitro Incidence Individual Investigation Late Onset Alzheimer Disease Latin America Latino Longitudinal Studies Mediating Medical Meta-Analysis Metabolism Mexican Mexico Minority National Institute on Aging Native Americans Native-Born North America Not Hispanic or Latino Participant Pattern Phenotype Population Population Heterogeneity Population Study Prevalence Research Risk Risk Factors Saliva Sample Size Sampling Survival Analysis Universities Validation Variant admixture mapping age group aged base case control cell repository cognitive testing cohort data sharing design endophenotype ethnic diversity experience experimental study follow-up genetic analysis genetic architecture genetic profiling genome sequencing genome wide association study genome-wide genomic data genomic locus innovation longitudinal analysis phenotypic data protective allele protective effect proteostasis rare variant tau Proteins whole genome

项目摘要

Abstract We aim to conduct traditional and innovative genetic analyses of whole-genome sequencing (WGS) data generated from a sub-sample of 3,500 participants from the Mexican Health Aging Study (MHAS). We have already been funded to collect saliva for DNA extraction and to perform genome-wide a association study in this Mexican sample (grant # R56-AG059756, PI: Tosto, Barral, Mayeux). Accumulating evidence supports a strong genetic component underpinning physiopathology of Late onset Alzheimer’s disease (LOAD). European population studies still dominate the pool of available genomic data resulting in a lack of generalizability of findings across diverse and minority populations. By 2020, the prevalence of dementia in Latin America will increase by 120%, compared to 49% in North America. It is therefore pivotal to increase representation of Hispanics and Latinos in genetic investigations. Mexicans are not currently represented in large genetic studies for LOAD. They show a unique genetic profile with one of the highest Native- American ancestral component percentages (~50%). This population may harbor unique LOAD risk/protective alleles, which are rare or absent in other populations. Furthermore, it may shed lights on the contribution of native ancestry on LOAD risk, which is still unknown. Our group has so far collected 9,162 saliva and blood samples from MHAS participants aged 60 and older and stored them at National Cell Repository for Alzheimer’s Disease (NCRAD). MHAS also provides a rich set of phenotypes (demographical, cognitive and medical assessment) with 20-years period of follow-up. The participants that will undergo whole genome sequencing (N~3,500 who meet clinical criteria for dementia and cognitively healthy; ratio 1:4) are characterized by an additional in-depth cognitive evaluation for which we have been already funded. The availability of extensive cognitive endophenotypes will facilitate a plethora of investigations beyond the classical case-control design (i.e. survival analyses and cognitive trajectories); it will ensure the accuracy of LOAD diagnosis, and will facilitate phenotype harmonization across different sequencing cohorts. We propose to: Aim 1) conduct traditional and innovative analysis of the whole genome sequence data generated in a sub-sample of 3,500 MHAS participants 60 years of age or older who meet diagnostic criteria for LOAD and healthy controls (ratio ~1:4); Aim 2) Conduct functional validation of genomic findings prioritized by WGS analyses; Aim 3) Share phenotypic and genomic data with the scientific community.

摘要