--- title: "The Familial Alzheimer Sequencing (FASe) project" id: "1262" type: "study" slug: "sa000004" published_at: "2020-02-19T18:56:58+00:00" modified_at: "2026-04-06T16:01:36+00:00" url: "https://dss.niagads.org/studies/sa000004/" markdown_url: "https://dss.niagads.org/studies/sa000004.md" excerpt: "GWAS studies were very successful in identifying genetic loci associated with AD risk. However, these studies could not point to the actual causal variant. In this study, WES and/or WGS data is being generated from families densely affected by Alzheimer..." --- ## Description GWAS studies were very successful in identifying genetic loci associated with AD risk. However, these studies could not point to the actual causal variant. In this study, WES and/or WGS data is being generated from families densely affected by Alzheimer disease (AD) under the hypothesis that these families will be enriched for rare genetic variants that confer risk to AD. This study included late onset families with a high proportion of AD cases (at least three affected members with DNA data available). The families originated from the NCRAD, NIA-LOAD, Knight-ADRC and DIAN-EXR cohorts. The proband of the family could not be a carrier of known pathogenic mutations in the Mendelian genes for AD (APP, PSEN1, PSEN2) or Frontotemporal Dementia (GRN, MAPT, C9ORF72). Cases within families had to be 65 years old or older at age at onset (AAO) and have a CDR >=0.5; controls within families had to have a CDR=0 at last assessment and be older than the largest AAO within the family. AD definition was based on a combination of both clinical and pathological information if available. Clinical diagnosis was overruled by pathological diagnosis. Subjects are Non-Hispanic white from North America, based on self-reporting. Autopsy information was provided if available, but it was not a requirement for enrollment. ## PI Carlos Cruchaga, Ph.D. *Washington University in St. Louis* Maria Victoria Fernandez, Ph.D. *Washington University in St. Louis* Oscar Harari, Ph.D. *Washington University in St. Louis* ## Associated Datasets - [NG00067 - ADSP Umbrella](https://dss.niagads.org/datasets/ng00067/) This dataset includes sequencing data and harmonized phenotypes from cohorts sequenced by the Alzheimer’s Disease Sequencing Project and other AD and Related Dementia’s studies. Samples are processed using a common… [Learn more](https://dss.niagads.org/datasets/ng00067/) ## Associated Sample Sets - [snd10004 - FASe Families WES](https://dss.niagads.org/sample-sets/snd10004/) FASe Family samples were sequenced at Genentech, MGI and Otogenetics on the HiSeq2000 machine. 715 samples were sequenced using the Agilent WES v5 capture region, 164 samples were using the… [Learn more](https://dss.niagads.org/sample-sets/snd10004/) - [snd10018 - FASe_Families WGS](https://dss.niagads.org/sample-sets/snd10018/) FASe_WGS samples were whole-genome sequenced at Broad either on the HiSeqX or HiSeq2000/2500 machine. Samples in either format (BAM files from hg37 build and FASTQ files) were sent to GCAD… [Learn more](https://dss.niagads.org/sample-sets/snd10018/) - [snd10101 - FASe-Families2 WGS](https://dss.niagads.org/sample-sets/snd10101/) 659 samples were sequenced by USUHS and Macrogen on the NovaSeq and Illumina HiSeq 2500 platform. GCAD received FASTQ and CRAM files for processing. A total of 646 samples passed… [Learn more](https://dss.niagads.org/sample-sets/snd10101/) ## Cohorts - [Knight Alzheimer’s Disease Research Center (KGAD)](https://dss.niagads.org/cohorts/knight-alzheimers-disease-research-center-kgad/) The search for novel risk factors for Alzheimer disease relies on access to accurate and deeply phenotyped datasets. The Memory and Aging Project at the Knight-ADRC (Knight ADRC-MAP) collects plasma,… [Learn more](https://dss.niagads.org/cohorts/knight-alzheimers-disease-research-center-kgad/) - [National Centralized Repository for Alzheimer’s Disease and Related Dementias Family (NCRAD Family)](https://dss.niagads.org/cohorts/national-centralized-repository-for-alzheimers-disease-and-related-dementias-family-ncrad-family/) The National Centralized Repository for Alzheimer’s Disease and Related Dementias (NCRAD) family cohort was started in 1990 and consists of families with two or more members with early or late… [Learn more](https://dss.niagads.org/cohorts/national-centralized-repository-for-alzheimers-disease-and-related-dementias-family-ncrad-family/) - [National Institute of Aging Alzheimer’s Disease Family Based Study (NIA AD-FBS)](https://dss.niagads.org/cohorts/national-institute-on-aging-late-onset-of-alzheimers-disease-family-nia-load/) The FBS collection is a longitudinal, multi-center late onset AD sibling genetics initiative. This NIA-funded study began in 2,002 and maintains DNA and cell lines on families with 2 or… [Learn more](https://dss.niagads.org/cohorts/national-institute-on-aging-late-onset-of-alzheimers-disease-family-nia-load/) - [University of Washington Families (RAS)](https://dss.niagads.org/cohorts/university-of-washington-families-ras/) 131 families with LOAD (751 individuals) were ascertained and evaluated through the University of Washington Alzheimer Disease Research Center. Clinical and neuropathological assessments of cases and controls, including blood sampling,… [Learn more](https://dss.niagads.org/cohorts/university-of-washington-families-ras/) ## Grants National Institutes of Health (R01-AG044546, P01-AG003991, RF1-AG053303, NIH P50-AG05681, P01-AG026276, U24-AG21886, U24-AG026395 and U01-AG058922) The Alzheimer Association (NIRG-11-200110, BAND-14-338165 and BFG-15-362540) ## Acknowledgement ### Acknowledgment statement for any data distributed by NIAGADS: Data for this study were prepared, archived, and distributed by the National Institute on Aging Alzheimer's Disease Data Storage Site (NIAGADS) at the University of Pennsylvania (U24-AG041689), funded by the National Institute on Aging. ### For investigators using The Familial Alzheimer Sequencing Project data: This work was supported by grants from the National Institutes of Health (R01AG044546, P01AG003991, RF1AG053303, R01AG058501, U01AG058922, RF1AG058501 and R01AG057777). The recruitment and clinical characterization of research participants at Washington University were supported by NIH P50 AG05681, P01 AG03991, and P01 AG026276. This work was supported by access to equipment made possible by the Hope Center for Neurological Disorders, and the Departments of Neurology and Psychiatry at Washington University School of Medicine. We thank the contributors who collected samples used in this study, as well as patients and their families, whose help and participation made this work possible. This work was supported by access to equipment made possible by the Hope Center for Neurological Disorders, and the Departments of Neurology and Psychiatry at Washington University School of Medicine ## Publications - Cruchaga C. **Polygenic risk score of sporadic late-onset Alzheimer's disease reveals a shared architecture with the familial and early-onset forms.***Alzheimer's & dementia : the journal of the Alzheimer's Association. 2018 Feb.*[PubMed link](https://pubmed.ncbi.nlm.nih.gov/28943286/) - Fernández MV. **Analysis of neurodegenerative Mendelian genes in clinically diagnosed Alzheimer Disease.***PLoS genetics. 2017 Nov.*[PubMed link](https://pubmed.ncbi.nlm.nih.gov/29091718/) - Ridge PG. **Linkage, whole genome sequence, and biological data implicate variants in RAB10 in Alzheimer's disease resilience.***Genome medicine. 2017 Nov 29.*[PubMed link](https://pubmed.ncbi.nlm.nih.gov/29183403/) - Fernández MV. **Evaluation of Gene-Based Family-Based Methods to Detect Novel Genes Associated With Familial Late Onset Alzheimer Disease.***Frontiers in neuroscience. 2018.*[PubMed link](https://pubmed.ncbi.nlm.nih.gov/29670507/)