Dataset Information

The National Institute on Aging Late-Onset Alzheimer's Disease Family Based Study: A resource for genetic discovery.

ABSTRACT:

Introduction

The National Institute on Aging Late-Onset Alzheimer's Disease Family Based Study (NIA-LOAD FBS) was established to study the genetic etiology of Alzheimer's disease (AD).

Methods

Recruitment focused on families with two living affected siblings and a third first-degree relative similar in age with or without dementia. Uniform assessments were completed, DNA was obtained, as was neuropathology, when possible. Apolipoprotein E (APOE) genotypes, genome-wide single nucleotide polymorphism (SNP) arrays, and sequencing was completed in most families.

Results

APOE genotype modified the age-at-onset in many large families. Novel variants and known variants associated with early- and late-onset AD and frontotemporal dementia were identified supporting an international effort to solve AD genetics.

Discussion

The NIA-LOAD FBS is the largest collection of familial AD worldwide, and data or samples have been included in 123 publications addressing the genetic etiology of AD. Genetic heterogeneity and variability in the age-at-onset provides opportunities to investigate the complexity of familial AD.

SUBMITTER: Reyes-Dumeyer D

PROVIDER: S-EPMC9250549 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The National Institute on Aging Late-Onset Alzheimer's Disease Family Based Study: A resource for genetic discovery.

Reyes-Dumeyer Dolly D Faber Kelley K Vardarajan Badri B Goate Alison A Renton Alan A Chao Michael M Boeve Brad B Cruchaga Carlos C Pericak-Vance Margaret M Haines Jonathan L JL Rosenberg Roger R Tsuang Debby D Sweet Robert A RA Bennett David A DA Wilson Robert S RS Foroud Tatiana T Mayeux Richard R

Alzheimer's & dementia : the journal of the Alzheimer's Association 20220103 10

<h4>Introduction</h4>The National Institute on Aging Late-Onset Alzheimer's Disease Family Based Study (NIA-LOAD FBS) was established to study the genetic etiology of Alzheimer's disease (AD).<h4>Methods</h4>Recruitment focused on families with two living affected siblings and a third first-degree relative similar in age with or without dementia. Uniform assessments were completed, DNA was obtained, as was neuropathology, when possible. Apolipoprotein E (APOE) genotypes, genome-wide single nucle ...[more]

PMID: 34978149

Similar Datasets

Project description:<p><b>Multiplex Family Study</b><br/>The purpose of the NIA Genetics Initiative: Multiplex Family Study is to identify families with multiple members diagnosed with late-onset Alzheimer's Disease. Families will be characterized clinically and blood samples will be collected to establish cell lines. If a blood sample is not available, autopsy samples will be collected for DNA extraction and storage. Our goal is to recruit 1,000 families over the course of the study. Clinical and demographic data from these families will be collected at the local site and coded data, without identifiers, will be sent and included in a national database of families with Alzheimer's Disease. This database, along with the biological samples, will be housed at the National Cell Repository for Alzheimer's Disease (NCRAD) at Indiana University. The Center or provider and the Cell Repository must sign a Material Transfer Agreement for shipment of biological samples and phenotypic data to NCRAD. The biological samples and data from these families will be available to qualified researchers, who must sign a Material Transfer Agreement before receiving DNA and data. An oversight committee known as the Cell Bank Advisory Committee (CBAC) will review and monitor the process of family identification and enrollment, data collection, the establishment of cell lines and access to samples.</p> <p><b>LOAD CIDR Project</b><br/>The first 362 families of the Multiplex Family Study (including 2,105 family members) were included in a 6K SNP genome-wide scan at the NIH-supported, Center for Inherited Disease Research (CIDR). An additional 297 unrelated, healthy controls were also genotyped at CIDR. The average age of onset of AD in the genotyped sample is 74 years and 62% of the sample is women. While primarily Caucasian, 3% are African-American, and 3% are of Hispanic ancestry. 72% of the families had at least 2 affected siblings, whereas 21% had 3 or more sampled affected individuals and 7% had 4 or more genotyped, affected family members.</p>

Project description:<p>Alzheimer disease is the most common neurodegenerative disorder of the elderly affecting an estimated five million Americans. Genetic factors contribute to the risk for disease with heritability estimates ranging from 57% to 79%. More than a decade ago, the ε4 variant of APOE was identified and remains the most consistently replicated genetic variant influencing the risk of late onset Alzheimer disease. A segregation analysis suggests there may be four additional genes influencing the age-at-onset of Alzheimer disease. In 2007 there were 968 association studies in 398 candidate genes reported, but none replicated consistently. There are many reasons for the lack of consistency, but one important reason for the lack of progress is the paucity of a sufficient number of well characterized families and patients available to the entire scientific community. The extensive effort and expense required to ascertain such a population has been addressed by the NIA-LOAD Family Study. Its goal is to identify and recruit families with two or more siblings with the late-onset form of Alzheimer's disease and a cohort of unrelated, non-demented controls similar in age and ethnic background, and to make the samples, the clinical and genotyping data and preliminary analyses available to qualified investigators world-wide. Genotyping by the Center for Inherited Disease Research (CIDR) was performed using the Illumina Infinium II assay protocol with hybridization to Illumina Human 610Quadv1_B Beadchips. This genotyping represents the largest collection of families ever assembled with Alzheimer's disease combining the NIA-LOAD Genetics Initiative Multiplex Family Study, the National Cell Repository for Alzheimer's Disease (NCRAD) with additional controls from the University of Kentucky. These genotyping results will serve as a focal point for future research that will identify all of the remaining genetic variants in Alzheimer's disease.</p>

Dataset Information

The National Institute on Aging Late-Onset Alzheimer's Disease Family Based Study: A resource for genetic discovery.

Introduction

Methods

Results

Discussion

Publications

The National Institute on Aging Late-Onset Alzheimer's Disease Family Based Study: A resource for genetic discovery.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets