Genomic Characterization of Alzheimer's Disease Risk in the Puerto Rican Population

波多黎各人群阿尔茨海默病风险的基因组特征

基本信息

批准号：
9194733
负责人：
Gary Wayne Beecham
金额：
$ 758.82万
依托单位：
UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-08-01 至 2021-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9194733
关键词：
Address African African American Alzheimer&apos s Disease Alzheimer&apos s disease risk Architecture Bioinformatics Caribbean Hispanic Chromosome Mapping Collection Communities Custom Data Data Set Disease Dominican Republic Elderly European Family Genetic Genetic Variation Genetic study Genome Genomic approach Genomics Genotype Goals Hispanics Individual Island Knowledge Large-Scale Sequencing Latino Minority Mutation Native Americans Not Hispanic or Latino Participant Pathway interactions Phase Population Prevalence Protocols documentation Puerto Rican Puerto Rico Race Resources Risk SNP array Testing Underrepresented Populations Variant Weight admixture mapping base case control density follow-up genetic epidemiology genetic linkage analysis genetic makeup genetic risk factor genetic variant genome sequencing identity by descent insight novel prevent protective effect response success targeted treatment therapeutic development whole genome

Address African African American Alzheimer&apos s Disease Alzheimer&apos s disease risk Architecture Bioinformatics Caribbean Hispanic Chromosome Mapping Collection Communities Custom Data Data Set Disease Dominican Republic Elderly European Family Genetic Genetic Variation Genetic study Genome Genomic approach Genomics Genotype Goals Hispanics Individual Island Knowledge Large-Scale Sequencing Latino Minority Mutation Native Americans Not Hispanic or Latino Participant Pathway interactions Phase Population Prevalence Protocols documentation Puerto Rican Puerto Rico Race Resources Risk SNP array Testing Underrepresented Populations Variant Weight admixture mapping base case control density follow-up genetic epidemiology genetic linkage analysis genetic makeup genetic risk factor genetic variant genome sequencing identity by descent insight novel prevent protective effect response success targeted treatment therapeutic development whole genome

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项目摘要

PROJECT SUMMARY To identify new treatment targets, we and others have examined the genomics of Alzheimer's disease (AD). However, genomic successes so far have arisen from studying primarily non-Hispanic White (NHW) participants, and the study of minority populations has been minimal. What few studies have been done in minority populations have suggested that the genetic architectures overlap, but only partially. Thus, studying minority populations not only serves to test generalization of the NHW findings but also provides a unique opportunity for discovery of novel targets and pathways. To begin addressing these issues, we propose here the Puerto Rico Alzheimer Disease and Related Disorders Initiative (PRADI). We will whole-genome sequencing (WGS) Caribbean Hispanic Puerto Rican (CHPR) AD multiplex families to identify novel AD variation in CHPRs, and to generalize existing AD genetic discoveries to this underrepresented population. This initiative will increase our knowledge about genetic variation, particularly for the Caribbean Hispanic population of Puerto Rico (CHPR). The Puerto Rican (PR) population is the 2nd largest Hispanic/Latino population in the continental US. The prevalence of AD in the Caribbean Hispanic population of the island of PR is estimated in 65,000. The PR population is a highly mixed population with average ancestry values of ~64% European, ~21% African, and ~15% Native American. The unique genetic make-up of the PR AD population will be critical in new discovery as well in replication of findings from the Alzheimer Disease Sequencing Consortium (ADSP) CHDR data and the Alzheimer's Disease Genetics Consortium (ADGC) African American (AA) data. Thus, discovery of genetic contributions to AD risk and protective variants in CHPR would have a substantial influence on our understanding of AD and towards our goal of identifying new treatment targets. Through this proposal in response to PAR-15-356 we will address this important issue by conducting genomic studies of AD in PR. Specifically we propose a family-based study in PR that parallels the family-based efforts in the ADSP Discovery phase and that will enhance and extend both current ADSP and ADGC efforts to a broader AD community. We aim to 1) Characterize the genetic epidemiology of AD in PR 2.) Generalize and refine known risk and protective loci in familial PR AD. 3.) Perform variant discovery in our PR AD families and case control data 4.) Leverage multi-ethnic populations (PR, DR and AA) to discover novel AD risk/protective effects by calculation of local ancestry, admixture mapping and bioinformatics analysis and 4.) Perform multi-locus analyses providing insight into functional implications of the risk and protective loci. Our overall goal is to identify targets for therapeutic development that will either prevent or significantly delay the onset of AD.

项目摘要为了确定新的治疗靶标，我们和其他人检查了阿尔茨海默氏病的基因组学（广告）。但是，迄今为止的基因组成功是由于研究主要是非西班牙裔白人（NHW）而产生的参与者，对少数族裔人口的研究很少。很少有研究少数族裔人群表明，遗传体系结构重叠，但仅部分是重叠的。因此，学习少数民族不仅可以测试NHW发现的概括，而且还提供了独特的发现新颖的目标和途径的机会。要开始解决这些问题，我们在这里提出波多黎各阿尔茨海默氏病和相关疾病倡议（PRADI）。我们将全基因组测序（WGS）加勒比海西班牙裔波多黎各人（CHPR）AD多重家族以识别新颖的广告 CHPR的差异，并将现有的AD遗传发现概括为这一代表性不足的人群。这项倡议将增加我们对遗传变异的了解，特别是对于加勒比海西班牙裔波多黎各的人口（chpr）。波多黎各人（PR）人口是美国大陆的第二大西班牙裔/拉丁裔人口。这 PR岛的加勒比西班牙裔人口中AD的患病率估计为65,000。公关人口是一个高度混血的人口，平均祖先价值约为64％，非洲约21％，并且〜15％的美国原住民。公关人群的独特遗传组成在新发现中至关重要以及复制来自阿尔茨海默氏病测序联盟（ADSP）CHDR数据的发现和阿尔茨海默氏病遗传学联盟（ADGC）非裔美国人（AA）数据。因此，发现遗传 chpr中对广告风险和保护性变体的贡献将对我们的我们产生重大影响了解AD并朝着我们确定新的治疗目标的目标。通过这个建议对PAR-15-356的反应我们将通过对PR进行AD的基因组研究来解决这一重要问题。具体而言，我们提出了一项基于家庭的PR研究，该研究与ADSP中的家庭努力平行发现阶段，这将增强和扩展当前的ADSP和ADGC努力，以更广泛的广告社区。我们的目标是1）表征PR 2中AD的遗传流行病学。家族公关中的风险和保护位点。 3.）在我们的公关广告家庭中执行变体发现和案例控制数据4.）利用多种族人口（PR，DR和AA）来发现新颖的AD风险/保护效应局部祖先，混合图和生物信息学分析的计算和4.）分析提供了对风险和保护基因座的功能含义的见解。我们的总体目标是确定可以预防或显着延迟AD发作的治疗开发目标。