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The National Institute on Aging (NIA) Late Onset of Alzheimer's Disease (LOAD) Family-Based Study (FBS)

美国国家老龄化研究所 (NIA) 晚发型阿尔茨海默病 (LOAD) 基于家庭的研究 (FBS)

基本信息

批准号：
9358127
负责人：
TATIANA M. FOROUD
金额：
$ 186.27万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-01 至 2022-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9358127
关键词：
Abbreviations Address Adult Children African American Age Aging Alzheimer&apos s Disease Autopsy Bibliography Biological Biological Markers Cells Central American Cerebrovascular Disorders Cessation of life Clinical Clinical Trials Clinical assessments Cognitive Collection Communities DNA Data Data Set Data Storage and Retrieval Development Diagnosis Elderly Ensure Ethnic group European Evaluation Family Family Study Family member Generations Genetic Genetic Research Genetic Variation Genetic study Genotype Goals Hereditary Disease Heritability Individual Institutes Late Onset Alzheimer Disease Lead Medical Genetics Mexican Americans Minority Recruitment Mutation National Human Genome Research Institute National Institute on Aging Nucleotides Participant Patients Penetrance Peripheral Blood Mononuclear Cell Phenotype Play Positioning Attribute Public Domains Publications RNA Race Recruitment Activity Research Research Personnel Resources Risk Risk Factors Role SNP array Sampling Sequence Analysis Siblings Site South American Specimen Standardization Time Tissues U-Series Cooperative Agreements United States Update Variant Whole Blood base brain tissue cohort database of Genotypes and Phenotypes disorder risk ethnic diversity exome exome sequencing follow-up genetic resource genetic variant genome wide association study genome-wide improved induced pluripotent stem cell member next generation non-demented novel marker offspring patient stratification proband programs repository research study trend virtual whole genome

项目摘要

The National Institute of Aging Late Onset Alzheimer’s Disease Family Based Study (NIA-LOAD FBS) began in 2003, starting a trend of greater cooperation and sharing of clinical and biological resources among researchers. To date, a total of 1,454 multiplex late onset AD (LOAD) families have been recruited with 8,543 family members clinically assessed and DNA sampled. We have also recruited 1,030 controls. Genome-wide SNP arrays have been generated on 5,428 individuals, exome chip genotyping on 1,278 individuals, whole exome sequencing in 1,484 and whole genome in 928 family members and controls. The conversion rate of to LOAD among unaffected relatives in the NIA-LOAD FBS is three-fold higher than would be expected among individuals of similar age (see #67 Bibliography). All of these data have been placed in the public domain in NIAGADS and dbGaP. The NIA-LOAD FBS is widely used in Alzheimer disease genetics with 79 high level publications to support this claim (Bibliography). The NIA-LOAD FBS provides an excellent opportunity to improve our understanding of the clinical and biological impact of genetic variation in the elderly. Phenotypic information is continually updated in these families by regular cognitive evaluations and autopsy at the time of death to confirm the diagnosis of LOAD. We have begun to recruit additional family members with a particular emphasis on the offspring generation. We have been able to bank brain tissue from family members creating one of the largest collections of brain tissues for familial LOAD. We will now expand biological sampling to include RNA and peripheral blood mononuclear cells in selected families. As additional genes and variants are identified, the members of the NIA LOAD Family Study will again play a central role as we explore: What is the impact of these risk and protective variants on disease risk? Are the genetic variants highly penetrant? What is the risk of developing LOAD in offspring? Can the presence of variants be used for stratification of patients into specific subtypes for clinical trials? Can the family data be used to identify novel biomarkers of disease risk, age at onset onset or progression? The NIA-LOAD FBS dataset is uniquely poised to address these clinical and biological questions because of its large size, rigorous ascertainment criteria, standardized clinical assessment and lack of restriction to specific mutations. Our efforts have made it easy and seamless for the genetic data to be shared, allowing even more researchers to obtain the data and samples collected as part of the NIA-LOAD FBS for research studies. This is by far the largest collection of LOAD families available in the world. Virtually every major genetic study of Alzheimer’s disease has included patients and controls from the NIA-LOAD FBS dataset. The availability of dense phenotypic and genetic data will also position the NIA-LOAD FBS in to determine the impact of variants identified in whole genome and whole exome sequencing projects currently underway.

美国国家衰老研究所晚发性阿尔茨海默病家族研究（NIA-LOAD FBS）