Alzheimer’s Disease Sequencing Project Consortia

Funded under several cooperative agreements and research grant awards, the Alzheimer’s Disease Sequencing Project (ADSP) involves more than 350 investigators from institutions across the globe. The ADSP is part of the NIA Alzheimer’s Disease Genetics Portfolio. The overarching goals of the ADSP are to:

Identify new genes involved in Alzheimer's disease (AD)
Identify gene alleles contributing to increased risk for or protection against the disease
Provide insight as to why individuals with known risk factor genes escape from developing AD
Identify potential avenues for therapeutic approaches and prevention of the disease

This study of human genetic variation and its relationship to health and disease involves a large number of study participants and will capture not only common single nucleotide variations but also rare copy number and structural variants that are increasingly thought to play an important role in complex disease.

Specific areas where researchers are focusing include:

Discover genes and loci that contain gene regulators
Determine the association of risk factor genes on disease progression
Determine the function of identified genes
Determine the influence of genes on specific disease biomarkers
Identify the underlying genetically driven molecular pathways
Determine why some individuals who have risk factor genes can escape the disease
Determine the differences in the Alzheimer’s genomic architecture among diverse populations
Genetically determine the subtypes of Alzheimer’s Disease to better classify subjects for targeted clinical trials
Determine the subtypes of the Alzheimer’s genome across diverse populations.

The ADSP is divided into several phases. Click to browse each phase.

Discovery Phase. Whole genome sequencing (WGS) and whole exome sequencing (WES) for the Discovery Phase are complete.
Discovery Extension Phase. WGS is complete for the Discovery Extension Phase. Data analysis is complete.
Follow-Up Study Phase. This phase began in 2017 and is to be completed in 2023.
Follow-Up Study 2.0 Diversity Initiative Phase. This phase began in 2022 and is to be completed in 2027.

Each of these components has a case-control and a family-based study design.

Applicants can obtain ADSP data for all phases of the ADSP from the NIAGADS Data Sharing Service (DSS):

Cleaned, quality control checked sequence data
Information on the composition of the study cohorts (e.g., case-control, family-based, and epidemiology cohorts)
Descriptions of the study cohorts included in the analysis
Accompanying phenotypic information such as age at disease onset, gender, diagnostic status, and cognitive measures
Epidemiological information such as educational level and certain demographic data available on the participants genotyped

Discovery Phase

The initial phase of the ADSP research plan is called the Discovery Phase. Samples were selected from well-characterized study cohorts of individuals with or without an AD diagnosis and the presence or absence of known risk factor genes. The National Human Genome Research Institute (NHGRI) provided funding for the sequencing.

The ADSP generated three sets of genome sequence data for these samples as part of the Discovery Phase:

WGS for 584 samples from 113 multiplex families
WES for 5,096 AD cases and 4,965 controls
WES of an enriched sample set comprised of 853 AD cases from multiply affected families and 171 Hispanic controls

Analysis of the Discovery Phase sequence data, supported by PAR-12-183 and RFA-HG-15-001, revealed many new variations in the genome that may be implicated as new genetic risk or protective factors in older adults at risk for AD. In February 2016, ADSP consultants recommended that subsequent sequencing and analysis be done on whole genomes in lieu of whole exome or targeted sequencing.

Additional information on ADSP activities can be found in RFA-AG-16-001 and RFA-AG-16-002.

Discovery Extension Phase

To further assess the genomes in multiply affected families, under funding provided by NHGRI, an additional approximately 430 samples were sequenced by the NHGRI-funded large-scale sequencing centers in a Discovery Extension Phase. This included 107 additional samples from families studied under the Discovery Phase, 207 samples from 77 new families, and 114 Hispanic controls.

Also under funding provided by NHGRI, additional participants were whole genome sequenced as part of the ADSP Discovery Case-Control Based Extension Study (1,000 each of non-Hispanic white, Caribbean Hispanic, and African American). This included 1,466 cases and 1,534 controls. A total of 739 autopsy samples were sequenced (500 non-Hispanic white and 68 African American cases and 164 non-Hispanic white and 7 African American controls).

Follow-Up Study Phase

The ADSP Discovery Phase has identified a number of variations in the genomes of individuals affected with AD. These findings are being pursued in the ADSP Follow-Up Study (FUS), funded solely by NIA. The long-term goals of the ADSP FUS are to:

Move the field closer to enabling a prediction of who will develop AD
Fully reveal the genetic architecture of AD in multiple ethnic groups
Better understand the underpinnings of AD pathogenesis
Aid the quest for therapeutic targets
Examine the AD genome in the ancestry of diverse populations

The ADSP Discovery Phase and the ADSP FUS are described under PAR-16-406. The ADSP FUS is leveraging existing infrastructure and collaborations to ensure continuity of ADSP participation. It provides funds for acquisition, archiving, sequencing, quality control, genome wide association studies (GWAS), and data sharing of a large number of samples from individuals affected by AD for WGS, as appropriate. Diverse ancestry continues to be a high ADSP priority. Well-phenotyped participants were selected with an emphasis on autopsy-confirmed and ancestry diverse cases/controls and the availability of longitudinal data. Funds are being provided for both sequencing and data analysis. This effort will pursue rare variants as comprehensively as possible, including consideration of statistical power, and exploration of a range of different populations containing those that are currently underrepresented in sequencing studies.

The majority of the samples from the ADSP Discovery and Discovery Extension phases were non-Hispanic white in origin, making the addition of ancestry diverse samples to the study critical to the identification of both shared and novel genetic risk factors for AD between populations. Collection and sequencing of ancestry diverse cohorts are emphasized in the ADSP FUS, to ensure additional existing cohorts with unrelated AD cases that encompass the richest possible ethnic diversity be given the highest priority for inclusion. For the United States, this includes augmenting African American, Hispanic, and Asian cohorts.

AD is not a single genetic entity; it is a genetic spectrum with a number of sub-phenotypes (endophenotypes). Endophenotypes will likely vary by ancestry. Important instances of ethnically unique AD/ADRD genetic variation have been identified in Hispanic and African American cohorts. Variants for AD are rare and can only be identified with a larger number of participants. Variants occur at different frequencies in different populations, and certain risk variants may be much easier to detect in some populations. ADSP studies in ethnic groups including African American and Hispanic, remain statistically underpowered, so the genetics of these populations remain largely unstudied. Therefore, a major effort is being undertaken to augment the numbers of cases and controls in ancestry diverse populations in the United States. In order to understand the underlying substructure of the diversity populations, global studies are a key component of this effort.

The global effort brings important population sectors that are not presently well represented in the ADSP including Korea, Australia, India, Central and South America, the Iberian Peninsula, and Africa. Examples of the expected types of sequencing and analytical assessments include continuing activities as outlined in the parent NOFOs (PAR-19-234 and PAR-17-214). Proposed approaches will not only increase the numbers of participants and the volume of data, but also will require novel methods to perform in-depth and subgroup analyses of diverse ethnic backgrounds, as well as integrated analyses to completely unravel the architecture of the AD genome.

To fulfill the goals of this ADSP FUS, eight existing cohorts of African American and pan-Hispanic ancestry, with a total of 13,745 samples (2,456 African American AD cases and 4,126 African American controls and 2,588 Hispanic AD cases and 4,475 Hispanic controls), were whole genome sequenced at The American Genome Center at the Uniformed Services University of the Health Sciences (USUHS) in coordination with existing NIH-funded AD infrastructure including the National Cell Repository for Alzheimer’s Disease (NCRAD), NIAGADS, and the Genome Center for Alzheimer’s Disease (GCAD). In addition, 1,500 non-Hispanic white autopsy cases and 1,500 controls have been sequenced. Brief descriptions of the cohorts selected for sequencing are provided below. Cohort collection, phenotypic characterization, and whole genome sequencing were funded by the National Institute on Aging.

In 2022, NIAGADS aims to release data generated under the initiative to support analysis on approximately 37,000 whole genomes to find novel genetic variants that modulate Alzheimer’s disease risk.

Follow-Up Study 2.0 Diversity Initiative Phase.

AD/ADRD is the leading cause of dementia in the elderly and occurs in all ancestry groups. The majority of genetic studies for AD/ADRD have been performed in non-Hispanic Whites (NHW) of European ancestry. In 2021, the NIA announced The Diverse Population Initiative (FUS 2.0, PAR-21-212) to address the need for a more diverse sample set within the ADSP. The long-term goals of the ADSP FUS 2.0 are consistent with the original study, but emphasize identifying therapeutic targets in a diverse population. FUS 2.0 is an international collaboration that aims to conduct whole-genome sequencing on 18,500 AD/ADRD cases and 18,500 controls each from African Americans and Africans, Hispanics, and Asians. Samples from the US, Africa, Mexico, and South America, and Asia will be obtained in order to reach statistical significance for rare variants in diverse ancestry populations.

A major barrier to participation in AD/ADRD genetic studies has been a lack of community-sensitive recruitment approaches that overcome historical mistrust of research participation. While recent studies have begun expanding into other populations, these populations are still under-represented in AD/ADRD genetics and genomics. The FUS 2.0 is striving to recruit new cohorts of diverse ancestry because a major component of the Diversity Initiative is to provide support to create resources for studying the genetic etiology of AD/ADRD in understudied and underserved populations.

A major goal of the FUS 2.0 initiative is to identify subtypes of AD/ADRD to help define the best therapeutic approaches in diverse populations and design better clinical trials. Through the efforts of the ADSP and other AD geneticists it is now certain that AD is not a single genetic entity; it is a genetic spectrum with a number of sub-phenotypes (endophenotypes). Endophenotypes will likely vary by ethnicity. Important instances of ethnically unique AD/ADRD genetic variation have been identified in Hispanic and African American cohorts. Variants for AD are rare and can only be identified with a larger number of participants. Genetic ancestry, independently or interacting with environmental/cultural factors, likely underlies at least part of this heterogeneity. Understanding the genomic architecture of diverse ancestry populations will help researchers to better identify genetically driven targets and to design better clinical trials.

FUS 2.0 follows on three other recent initiatives to enhance the ADSP’s capability to identify new risk and protective genes:

The Phenotype Harmonization Consortium is aggregating and harmonizing clinical, cognitive, imaging, and biomarker phenotype data from all participating ADSP cohorts.
The Functional Genomics Consortium (FGC) is generating “omics” experimental data to further characterize ADSP genetic findings and to help better define subtypes of Alzheimer’s and related dementias.
The Artificial Intelligence/Machine-Learning Consortium employs sophisticated computational methods to further integrate and analyze ADSP data and optimize subject selection for clinical trials based on participants’ genetic characteristics.

ADSP FUS and FUS 2.0 Cohort Descriptions

Additional cohorts will be added as the study progresses.

The A4 Study was designed as a three-year, placebo-controlled, randomized clinical trial to test whether anti-amyloid treatment can slow the rate of cognitive decline in older individuals from diverse ethnic-racial backgrounds (non-Hispanic White, African American and Latino/Hispanic) with evidence of amyloid accumulation on screening PET scans. The ADSP-FUS has sequenced over 3,400 participants from the study.
The Alzheimer’s Disease Center (ADC) Cohorts, which includes Black/African American, Amerindian, and Latino/Hispanic specific cohorts, selected from the National Institute on Aging’s ADRC’s, a network of 38 academic centers across the US focused on AD and ADRD research.
The Alzheimer’s Disease Research Center Autopsy (ADRC) Cohort includes 1,500 cases with autopsy and 1,372 controls from the National Institute on Aging’s ADRC’s. These individuals are well phenotyped and increase the currently underpowered non-Hispanic White sample with WGS data from the ADSP Discovery and Discovery Extension Phases (1,212 cases and 524 controls).
The Alzheimer’s Disease Genetics Consortium (ADGC) African-American Cohort, is a cohort of 1,240 cases and 1,643 controls collected from several cohorts including from the GenerAAtions Study, Indianapolis-Ibadan Study, Rush University, University of Miami, Case Western Reserve University, North Carolina A & T University, and The Mirage Study.
The Amish Protective Variant Study, based at Case Western Reserve University and the University of Miami (Cummings et al. 2012; D’Aoust et al. 2015), is being conducted in the Indiana and Ohio Old Order Amish population. This population is an isolated founder population originating from immigration of German and Swiss Anabaptists to the United States in the 1700’s and 1800’s. Approximately 840 individuals from the study have been sequenced and included in the ADSP-FUS.
The ASPREE STUDY (ASPirin in Reducing Events in the Elderly) was an international, randomized, placebo-controlled trial funded by the NIH to determine whether daily low dose aspirin (100 mg) increased survival, free of dementia or physical disability, for healthy older people (>60 years of age) without a history of cardiovascular disease, dementia or significant physical disability at enrollment. It included 19,114 healthy older individuals and the initial completion was in 2018 (McNeil 2018). ASPREE-eXTension (ASPREE-XT) study, funded by the NIA, is an observational follow-up of the same cohort that will be extended from 2019 through 2024. ASPREE and ASPREE-XT has and will continue to determine factors, such as those related to lifestyle, health behavior, environment, genes, blood biomarkers and many others, that may be predictors of good health and longevity or predispose to age-related diseases, but is especially focused upon dementia and cognitive decline.
The Case Western Reserve University (CWRU) Autopsy Cohort was an ADRC clinic-based sample. Medical records are available on all cases and controls, all of whom were tested before death for cognitive function.
The Case Western Reserve University (CWRU) Rapid Decline Cohort (Cohen et al. 2015) represents patients with rapid decline. Through the National Prion Disease Pathology Surveillance Center, CWRU has identified 300+ aged individuals who have classical AD pathology upon autopsy but whose course is very short: from six months to three years. This course is more typical of a prion disease; however, these individuals have been tested for and do not have any prion disease. The amyloid in the amyloid plaques has a slightly different protein structure, suggesting that that rpAD has a different genetic architecture than typical late-onset AD (LOAD). Additionally, sequencing of the APP gene did not identify any novel or known pathogenic variation. rpAD has not been genetically examined and the 300+ autopsy confirmed AD cases would significantly increase the pool of confirmed cases. Substantial clinical data are available on most cases, and additional samples of blood, plasma, CSF and RNA are available on a subset, greatly increasing their potential value.
The Center for Cognitive Neuroscience and Aging (CNSA) at the University of Miami is a center focused on the evaluation, management, treatment and care for older persons and their families with memory and other brain disorders affecting cognition. 343 individuals from CNSA have been sequenced and included in the ADSP-FUS.
The Cuban American Alzheimer’s Disease Initiative (CuADI) is a convenience sample ascertained through community outreach to Alzheimer’s and adult day care centers in Southern Florida, lay conferences, and Neurology and Memory Disorders clinics. All participants underwent a standard protocol which included collection of sociodemographic information, detailed clinical history, and cognitive screening (3MS). In addition, behavioral measures (GDS, CSDD, and NPI-Q) and functional (ADL) assessments are available. Standard neurocognitive data is available on all individuals.
The Estudio Familiar de Influencia Genetica en Alzheimer (EFIGA) Study is a study of late-onset AD patients with Caribbean-Hispanic ancestry being conducted at Columbia University’s Taub Institute for Research on Alzheimer’s Disease and the Aging Brain in New York City (Vardarajan et al. 2014). Families and unrelated individuals were recruited as a part of a family-based study: Estudio Familiar de Influencia Genetica en Alzheimer, based in the Dominican Republic. All individuals undergo standard neuropsychological tests and neurological examinations to verify their clinical status and for diagnoses based on NINCDS-ADRDA criteria for probable or possible LOAD.
The ADGC Early Onset Alzheimer Disease (EOAD) Cohort is a sample set consisting of ~1,400 EOAD cases available through the Alzheimer Disease Genetics Consortium (ADGC). All samples are early onset (age at onset <65), with available DNA and phenotyping (through the Uniform DataSet). This sample set is expected to have minimal known mutations (APP, PSEN1, PSEN2, SORL1 etc). A significant subset of the sample has autopsy information and/or information on family history providing the opportunity to generalize variants identified to neuropathological endophenotypes and to assess whether variants identified are unique to families multiply affected by the disease or also play a role in sporadic EOAD.
The Gwangju Alzheimer’s and Related Dementias (GARD) Cohort is a prospectively followed sample of persons in a senior citizen’s community located in the South Korean southwestern city of Gwangju. A large portion of the cohort has been evaluated with the Seoul Neuropsychological Screening Battery (SNSB) and had a brain MRI scan, and some participants have had PET-amyloid imaging. Previous studies of this cohort include GWAS for AD (Kang et al. J Alzheimers Dis. 2021; 82(4):1451-1460) and brain MRI traits (Park et al. Transl Psychiatry 2021; 11:590). Another study identified a SNP in the APOE promoter that modifies the effect of the ε4 allele and may explain differences in the AD/ε4 across East Asians, Caucasians and African Americans (Choi et al. J Clin Med 2019; 8:1236). Whole genome sequencing is being performed for 4,000 subjects (2,000 AD cases and 2,000 controls. The GARD sample will be among the largest Asian cohorts with WGS data.
Interaction between SARS-CoV-2 Infection and Ancestral genomic Variations in the Risk of Alzheimer's Disease and Related Disorders (ISAVRAD). ISAVRAD is a longitudinal study of older adult Amerindians from Northern Argentina with or without exposure to SARS-CoV-2 infection to understand the impact of interactions between ancestral genomic variants and infection on the risk of cognitive decline and ADRD. With funding from the Alzheimer's Association and Fundacion FULTRA, 875 participants over 60 years of age and without pre-infection cognitive impairment were enrolled during the first 18 months of the pandemic; collected data include exhaustive clinical phenotypes, detailed cognitive assessments, plasma for biomarkers and WGS. Additional studies including neuroimaging and expanding the sample to Yoruba participants from Ibadan (Nigeria), Latino participants from the Bronx (New York), Mexican-American participants from Laredo and San Antonio (Texas), and non-tribal Native Americans from Kings County (Washington) are planned.
Korean Brain Aging Study for the Early Diagnosis and Prediction of AD (KBASE) is a prospective cohort study launched at Seoul National University (SNU) in 2014 using a similar design and methods as the North American Alzheimer’s Disease Neuroimaging Initiative (ADNI). The KBASE cohort consists of well-characterized participants including cognitively normal (CN) controls with a wide age range (20 to 90 years) and older adults with mild cognitive impairment (MCI) or AD dementia (AD). KBASE included longitudinal collection of clinical, cognitive and lifestyle data, multimodal MRI and PET (amyloid, tau and FDG) neuroimaging, and bio-specimens in Korea during the first phase (“KBASE1”). KBASE2 represents a collaboration between the ADSP, Indiana University, the KBASE team at SNU, USC/LONI and UPENN. Over 1000 whole genome sequences (WGS) of Korean participants will be contributed to the ADSP, and the extensive ADSP multi-ethnic data set will be analyzed. KBASE2 will expand the cohort and continue longitudinal data and sample collection and provide WGS and data harmonization and sharing, analyze longitudinal amyloid, tau, neurodegeneration and vascular (A/T/N/V) imaging biomarkers and analyze multi-omics data for association with A/T/N/V biomarkers for AD to identify dysregulated gene modules and pathways.
LASI-DAD: The Harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD) is a national representative cohort of 4,096 adults 60 years of age and older in India across 18 states and union territories. LASI-DAD is an in-depth study on cognitive aging and dementia drawn from the larger Longitudinal Aging Study in India (LASI). Whole genome sequencing of 2,712 individuals has been completed. These data can be linked to the Harmonized LASI and Harmonized LASI-DAD datasets, offering the opportunity for researchers to gain insight into the aging population in India.
Mexican APP/PSEN Study
The Mexican Health and Aging Study (MHAS) sponsored by the National Institutes of Health (NIH) National Institute on Aging (NIA), is prospective study of health and aging in Mexico that began in 2001 (MHAS 2001). The ADSP FUS will sequence 200 MHAS cases and 2,600 MHAS controls from this study starting in 2019.
The University of Miami Brain Bank Cohort was ascertained through self-referred cases and controls to the University of Miami Brain Endowment Bank, a National Institutes of Health (NIH) NeuroBioBank, one of six designated brain and tissue biorepositories in the nation. Medical records are available on all cases and controls, all of whom were tested before death for cognitive function.
The University of Miami John P. Hussman Institute for Human Genomics (HIHG) Brain Bank is a clinic and community outreach sample ascertained in North Carolina, South Carolina and Virginia. The HIHG Brain Bank autopsy individuals followed the typical clinical course of disease.
The Northern Manhattan Study (NOMAS), funded by the NIH’s NINDS, is a study focused on stroke or related neurological syndromes (Sacco et al. 2004). The ADSP FUS will sequence 88 Hispanic cases and 175 Hispanic controls, and 22 African-American cases and 43 African-American controls from this study starting in 2020.
The Peru Alzheimer’s Disease Initiative (PeADI) is being conducted at several sites in Peru including Lima (Marca-Ysabel et al. 2021). The Mestizo population living in Lima, the capital city, is comprised of ~76% of Amerindian, 11% Southern European, and 3% Northern African ancestries, and a smaller proportion of western central Africa, western central Europe, Finland, northern Siberia and Jewish diaspora. Cases will be clinic based and controls will be clinic and community based. With few Amerindian individuals available for study, the inclusion of a Peruvian cohort will enhance the admixture studies proposed in CADRE and other groups in the ADSP analysis phase.
The Puerto Rican 10/66 Study, is an Alzheimer’s Disease International study of dementia in Puerto Rico that began in 2007 (Prince et al. 2007). The ADSP FUS has sequenced ~1560 individuals from this study.
The Puerto Rican Alzheimer’s Disease Initiative (PRADI) is an NIA study of late-onset Alzheimer disease focused on the Caribbean-Hispanic Puerto Rican population. The ADSP FUS began sequencing 500 cases and 500 controls from this study starting in 2020.
The Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study is a national study of risk factors for stroke in adults 45 years old or older that includes measurements of traditional stroke risk factors such as blood pressure and cholesterol levels, and an echocardiogram of the heart (Longstreth 2006). The ADSP FUS will sequence 1,000 African American cases and 1,500 African American controls from this study starting in 2018.
The Research in African-American Alzheimer’s Disease Initiative (REAAADI) is a NIH NIA study focused on identifying genetic factors for Alzheimer disease within the African-American population in order to detect new targets for drug development and improve accessibility to Alzheimer’s disease education within the community. The ADSP FUS will sequence 300 cases and 300 controls from this study starting in 2020.
The Stanford (STeP) cohort contains samples from Brains for Dementia Research (BDR) Genetics project (Dr. Kevin Morgan, PI and Directory of the Alzheimer’s Research UK (ARUK) DNA Consortium and BDR) (Francis et al. 2018). The BDR cohort and program was for planned brain donation across five UK brain banks and one donation point, with standardized operating procedures, following longitudinal clinical and psychometric assessments for people with no cognitive impairment as well as those with dementia. See the Francis et al. publication for a detailed description about the BDR cohort set-up, clinical data, and psychometric assessment measures collected.
The Texas Alzheimer’s Research and Care Consortium (TARCC) includes cases enrolled at several major medical research institutions including Baylor College of Medicine, Texas Tech University Health Sciences Center, University of North Texas Health Science Center, The University of Texas Health Sciences Center at San Antonio, The University of Texas Southwestern Medical Center, and Texas A & M Health Science Center. Individuals must be at least 55 years of age with a diagnosis of probable AD or normal cognition. Information is obtained from the clinical and neurological examination on age at onset of symptoms (if AD patient), family history of dementia in first degree relatives, cardiovascular disease and cardiovascular disease risk factors. Subjects also undergo a battery of neuropsychological tests.
The Wisconsin Registry for Alzheimer’s Prevention (WRAP) Study is comprised of individuals from a registry begun in 2011 that includes more than 1,700 individuals, followed over time, to learn about biological, health, and lifestyle factors that may affect Alzheimer’s disease. The data set includes information on cognition, lifestyle, physical activity, biomarkers, genetics and metabolism.

Research Conducted with ADSP Data

View a list of publications.

Some Additional ADSP Collaborations

Alzheimer’s Disease Neuroimaging Initiative (ADNI)
International Genomics of Alzheimer's Project (IGAP)
Long Life Family Study (LLFS)
The Reykjavik Study (Iceland)
The VA Million Veteran Program
Individually funded investigators and other organizations/websites designed to store and distribute data related to AD

ADSP FUS Sequencing, Quality Control, and Data Sharing

The workflow for the acquisition, processing, and sharing of data from the ADSP Follow-up Study is:

ADSP investigators identify, assemble, and send DNA samples from well-phenotyped participants affected with AD for WGS to NCRAD.
NCRAD receives and prepares DNA, performs quality control checks, retains aliquots of DNA, plates and ships samples to sequencing centers, and tracks samples through the sequencing process.
NCRAD acquires and archives appropriate documentation for compliance of sample and data handling with NIH policy and ensures that standard operating procedures for sample handling are followed.
Sequencing centers perform GWAS and WGS and process sequence data.
GCAD receives and processes data and performs quality control checks, variant calling, and harmonization with other ADSP data, and provides this processed data to NIAGADS.
NIAGADS receives and manages the WGS and GWAS datasets and coordinates ADSP phenotype and GWAS data collection, sequence data production, and delivery to the research community.

In order to meet time constraints, financial considerations, and the milestones provided under the National Alzheimer's Project Act (NAPA), sequence data from unaffected participants were drawn from existing WGS data from sequencing projects performed in large, well-characterized age-matched cohorts with documented appropriate cognitive function testing. Samples from AD participants were selected from existing cohorts and sample sets where possible. Samples come from all types of epidemiology study designs, existing case/control, family-based, and other sample sets where AD is the underlying form of dementia. Collection of samples, genetic sequencing, quality control, variant calling, and data harmonization are supported under RFA-AG-16-001, PAR-16-406, PAR-19-288, and PAR-20-110.

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