The Origins of Alzheimer Disease in African Americans

非裔美国人阿尔茨海默病的起源

基本信息

批准号：
10704751
负责人：
Rufus Olusola Akinyemi
金额：
$ 520.85万
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：
2022
资助国家：
美国
起止时间：
2022-09-15 至 2027-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10704751
关键词：
Admixture Africa African African American African American population African ancestry Alzheimer&apos s Disease Alzheimer&apos s disease risk Astrocytes Attitude Autopsy Awareness Biological Markers Brain CRISPR/Cas technology Cardiovascular Diseases Cardiovascular system Caribbean Hispanic Case/Control Studies Chromosome 5 Clinical Data Data Set Decision Making Dementia Detection Diagnosis Disease Disease susceptibility Education Elderly Enrollment Ethnic Population European ancestry Family Family Study Family member Frequencies Genes Genetic Genetic Diseases Genetic Predisposition to Disease Genetic Risk Genetic Variation Genetic study Genomics Geographic Locations Goals Heritability Heterogeneity High Prevalence Individual Induced pluripotent stem cell derived neurons Measures Microglia Molecular Neurocognitive Neuropsychology Not Hispanic or Latino Pattern Phenotype Plasma Population Prevention Prevention strategy Research Design Risk Role Rural Community Sample Size Sampling Testing Tissue Donations Trust Underrepresented Populations Underserved Population Urban Community Variant brain tissue cohort data integration design disease phenotype druggable target epigenomics gene discovery genetic architecture genetic risk factor genome sequencing genome wide association study health data improved induced pluripotent stem cell interest novel phenotypic data precision medicine programs protective factors racial population rare variant risk prediction risk variant social health determinants tool transcriptomics whole genome

项目摘要

ABSTRACT The goal of this proposal is to advance our understanding of the genetic etiology of Alzheimer disease (AD) risk in understudied and underserved populations. AD is the leading cause of dementia in the elderly and occurs in all ethnic and racial groups, but most genetic studies for AD have been performed in non-Hispanic Whites (NHW) of European ancestry. This is problematic, as much smaller studies in African Americans (AA), who have a higher prevalence of AD compared to NHW, have already revealed differences in risk effect sizes in known loci (e.g., APOE; ABCA7), indicating multiple unique patterns of risk. Genetic ancestry (including variability in allele risk frequencies and population specific variants modifying known and novel risk loci), in addition to environmental/cultural factors and their interactions with genetic risk, likely underlies part of this heterogeneity. With only a small number of the whole genome sequences in the Alzheimer’s Disease Sequencing Project (ADSP) coming from AA, increased sample sizes and multiple study designs are needed to elucidate risk in diverse ancestral populations. Family studies provide a powerful complementary design to case- control studies that can enhance risk prediction and the detection of novel rare risk variants. Filling these critical gaps using genetic tools will enhance our understanding of AD risk and provide the basis for identifying prevention strategies and druggable targets. Including ancestral populations from Africa in particular a unique cohort of multiplex African AD families enables dissecting risk not only in African populations but also among all populations with AF ancestry. Our efforts will allow for improved disease prediction, prevention, diagnosis, and treatment through precision medicine, in AA, African, and other African admixed populations.

抽象的该提案的目标是增进我们对阿尔茨海默病遗传病因学的理解 AD 风险在研究不足和服务不足的人群中是导致老年人痴呆的主要原因。并发生在所有民族和种族群体中，但大多数 AD 基因研究都是在非西班牙裔人群中进行的欧洲血统的白人 (NHW) 这是有问题的，因为针对非裔美国人 (AA) 的研究规模较小。与 NHW 相比，AD 患病率更高，已经揭示了风险效应大小的差异已知基因座（例如 APOE；ABCA7），表明多种独特的风险模式（包括。等位基因风险频率的变异性和修改已知和新风险位点的群体特异性变异），除了环境/文化因素及其与遗传风险的相互作用之外，可能是其中的一部分阿尔茨海默病的全基因组序列仅有少量。来自 AA 的测序项目 (ADSP)、需要增加样本量和多项研究设计阐明不同祖先群体的风险，家庭研究为案例提供了强有力的补充设计。对照研究可以增强风险预测和新型罕见风险变异的检测。使用遗传工具的差距将增强我们对 AD 风险的理解，并为识别 AD 风险提供基础预防策略和药物目标尤其包括来自非洲的独特人群。多重非洲 AD 家族队列不仅可以分析非洲人群的风险，还可以分析所有人群的风险我们的努力将改善疾病的预测、预防、诊断和治疗。通过精准医学对 AA、非洲人和其他非洲混合人群进行治疗。