The ADGC is a large U.S. based consortium formed to collaboratively use the collective resources of the AD research community to resolve Alzheimer’s disease (AD) genetics.

Working with the National Alzheimer’s Coordinating Center (NACC), and the National Centralized Repository for Alzheimer’s Disease and Related Dementias (NCRAD), the ADGC identifies well-characterized AD/ADRD patients and cognitively unaffected controls from the Alzheimer’s Disease Research Centers (ADRCs). The ADGC collaborates with numerous other studies to generate a large multiethnic subject collection, with harmonized genetic and phenotype data in order to perform coordinated analyses of both early and late-onset AD genetics. The ADGC generates or acquires genome-wide array data for all cohorts, and whole genome sequence (WGS) and whole exome sequence (WES) data when possible.

Alzheimer’s Disease Research Centers GWAS Datasets (ADC1-15):

National Institute on Aging’s Alzheimer’s Disease Research Center (NIA-ADRC) Samples: The National Institute on Aging (NIA) funds Alzheimer’s Disease Research Centers (ADRCs) at major medical institutions across the United States. The ADRCs mission is to translate research advances into improved care and diagnoses. Researchers at these Centers are contributing to finding treatments and prevention of Alzheimer’s Disease and related dementias.

The NIA ADRC cohort includes subjects ascertained and evaluated by the clinical and neuropathology cores of the past and 33 presently NIA-funded ADRCs. Data collection is coordinated by the National Alzheimer’s Coordinating Center (NACC). NACC coordinates collection of phenotype data from the ADRCs, cleans all data, coordinates implementation of definitions of AD cases and controls, and coordinates collection of samples. The ADRC cohort consists of neuropath, clinical, and autopsy-confirmed AD cases, cognitively normal elders (CNEs) with complete neuropathology data who were older than 60 years at age of death and living CNEs evaluated using the Uniform dataset (UDS) protocol who were documented to not have mild cognitive impairment (MCI) and were between 60 and 100 years of age at assessment.

Based on the data collected by NACC, ADSP Phenotype Harmonization Consortium (ADSP-PHC) derived inclusion and exclusion criteria for AD and control samples. Clinical AD cases were demented according to NACC’s cognitive status of dementia at UDS visit with a primary etiologic diagnosis of Alzheimer’s Dementia. Controls did not meet dementia or MCI criteria and exhibited no etiologic diagnoses. Neuropathologic definition of cases and control followed NIA-AA Alzheimer’s disease neuropathologic change (ADNC) scores (ABC method), with intermediate or higher ADNC scores classified as Cases and low ADNC scores labeled Controls. When ADNC scores were not available, a similar approach was used with BRAAK and CERAD scores, with Cases possessing a BRAAK Stage greater than or equal to III and a CERAD score of either moderate or frequent neuritic plaques. Consistent with the ADNC definition, if a participant was lower on BRAAK or CERAD they were given a Control diagnosis (equivalent to a low score on ADNC). Individuals missing an ADNC score and either BRAAK or CERAD score were not given a neuropathologic diagnosis. Persons with Down’s syndrome, neuropsychiatric, neurodegenerative, and neurologic disorders, brain structure abnormalities, non-AD tauopathies and synucleinopathies were excluded from both clinical and autopsy diagnoses of cases and controls. All autopsied controls had a clinical evaluation within two years of death. An autopsy-confirmed variable was derived from matching neuropath and clinical diagnoses when available. All cases and controls were required to be >60 years of age.

DNA was prepared by the National Centralized Repository for Alzheimer’s Disease and Related Dementias (NCRAD) for genotyping and sent to the genotyping site at Children’s Hospital of Philadelphia. ADC samples were genotyped and analyzed in separate batches.

ADGC African American Dataset:

The Alzheimer’s Disease Genetics Consortium (ADGC) selected subjects from the National Institute on Aging (NIA) Alzheimer‘s Disease Centers (ADCs), the University of Miami/Duke University, the Multi-Institutional Research in Alzheimer’s Genetic Epidemiology (MIRAGE) Study, the Rush University Religious Orders Study (ROS) and Memory and Aging Project (MAP), and the Genetic and Environmental Risk Factors for Alzheimer’s Disease Among African Americans (GenerAAtions) Study. All individuals self-identified as African American and had a minimum age of 60 years at onset (cases) or last exam (cognitively-normal controls). The case and control status of subjects is based on the National Institute of Neurological and Communicative Disorders and Stroke—Alzheimer’s Disease and Related Disorders Association criteria. The John P. Hussman Institute for Human Genomics (HIHG) at the University of Miami Miller School of Medicine performed whole exome sequencing on 3200 samples. The Genome Center for Alzheimer’s Disease (GCAD) at the University of Pennsylvania processed the data using their standardized pipeline.

Texas Alzheimer’s Research and Care Consortium (TARCC):

Data from the Texas Alzheimer’s Research and Care Consortium (TARCC) includes cases enrolled at several major medical research institutions (as of 2013 this included 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 based on a Clinical Dementia Rating Global Score of 0. Clinical, neurological, and neuropsychological examinations performed at each site follow the TARCC research protocol that has been adopted from the standard clinical work-up for dementia. All subjects are examined at baseline and at each annual follow-up visit.

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 as part of the TARC research protocol, with all information reviewed by a consensus panel made up of at least a physician, neuropsychologist, and research coordinator at each site to assign the final clinical diagnosis according to NINCDS-ADRDA criteria.

Genotyping of the cohort was supported by the ADGC and performed by the Center of Applied Genomics (CAG) at the Children’s Hospital of Philadelphia (CHOP). The ADGC selected non-Hispanic whites and Hispanic TARCC AD and cognitively normal subjects for whole genome sequencing (WGS). WGS was performed by the Uniformed Services University of the Health Sciences (USUHS).

Gerard D. Schellenberg, Ph.D.

Lindsay A. Farrer, Ph.D.

Jonathan L. Haines, Ph.D.

Richard P. Mayeux, MD, MSc

Margaret A. Pericak-Vance, Ph.D.

ADGC NIA grant U01 AG032984

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 Alzheimer’s Disease Genetics Consortium data:

Use the following for use of any ADGC generated data:

The Alzheimer’s Disease Genetics Consortium (ADGC) supported sample preparation, sequencing and data processing through NIA grant U01AG032984. Sequencing data generation and harmonization is supported by the Genome Center for Alzheimer’s Disease, U54AG052427, and data sharing is supported by NIAGADS, U24AG041689. Samples from the National Centralized Repository for Alzheimer’s Disease and Related Dementias (NCRAD), which receives government support under a cooperative agreement grant (U24 AG021886) awarded by the National Institute on Aging (NIA), were used in this study. We thank contributors who collected samples used in this study, as well as patients and their families, whose help and participation made this work possible.

See below for additional dataset specific acknowledgments:

For use with GWAS Datasets ADC1-15:

The NACC database is funded by NIA/NIH Grant U24 AG072122. NACC data are contributed by the NIA-funded ADRCs: P30 AG062429 (PI James Brewer, MD, PhD), P30 AG066468 (PI Oscar Lopez, MD), P30 AG062421 (PI Bradley Hyman, MD, PhD), P30 AG066509 (PI Thomas Grabowski, MD), P30 AG066514 (PI Mary Sano, PhD), P30 AG066530 (PI Helena Chui, MD), P30 AG066507 (PI Marilyn Albert, PhD), P30 AG066444 (PI John Morris, MD), P30 AG066518 (PI Jeffrey Kaye, MD), P30 AG066512 (PI Thomas Wisniewski, MD), P30 AG066462 (PI Scott Small, MD), P30 AG072979 (PI David Wolk, MD), P30 AG072972 (PI Charles DeCarli, MD), P30 AG072976 (PI Andrew Saykin, PsyD), P30 AG072975 (PI David Bennett, MD), P30 AG072978 (PI Neil Kowall, MD), P30 AG072977 (PI Robert Vassar, PhD), P30 AG066519 (PI Frank LaFerla, PhD), P30 AG062677 (PI Ronald Petersen, MD, PhD), P30 AG079280 (PI Eric Reiman, MD), P30 AG062422 (PI Gil Rabinovici, MD), P30 AG066511 (PI Allan Levey, MD, PhD), P30 AG072946 (PI Linda Van Eldik, PhD), P30 AG062715 (PI Sanjay Asthana, MD, FRCP), P30 AG072973 (PI Russell Swerdlow, MD), P30 AG066506 (PI Todd Golde, MD, PhD), P30 AG066508 (PI Stephen Strittmatter, MD, PhD), P30 AG066515 (PI Victor Henderson, MD, MS), P30 AG072947 (PI Suzanne Craft, PhD), P30 AG072931 (PI Henry Paulson, MD, PhD), P30 AG066546 (PI Sudha Seshadri, MD), P20 AG068024 (PI Erik Roberson, MD, PhD), P20 AG068053 (PI Justin Miller, PhD), P20 AG068077 (PI Gary Rosenberg, MD), P20 AG068082 (PI Angela Jefferson, PhD), P30 AG072958 (PI Heather Whitson, MD), P30 AG072959 (PI James Leverenz, MD). NACC phenotypes were provided by the ADSP Phenotype Harmonization Consortium (ADSP-PHC), funded by NIA (U24 AG074855, U01 AG068057 and R01 AG059716).

For use with the ADGC_AA_WES (snd10003) data:

NIH grants supported enrollment and data collection for the individual studies including: GenerAAtions R01AG20688 (PI M. Daniele Fallin, PhD); Miami/Duke R01 AG027944, R01 AG028786 (PI Margaret A. Pericak-Vance, PhD); NC A&T P20 MD000546, R01 AG28786-01A1 (PI Goldie S. Byrd, PhD); Case Western (PI Jonathan L. Haines, PhD); MIRAGE R01 AG009029 (PI Lindsay A. Farrer, PhD); ROS P30AG10161, R01AG15819, R01AG30146, TGen (PI David A. Bennett, MD); MAP R01AG17917, R01AG15819, TGen (PI David A. Bennett, MD); MARS R01AG022018 (PI Lisa L. Barnes).[CL1] [KA2] The NACC database is funded by NIA/NIH Grant U24 AG072122. NACC data are contributed by the NIA-funded ADCs: P30 AG019610 (PI Eric Reiman, MD), P30 AG013846 (PI Neil Kowall, MD), P30 AG062428-01 (PI James Leverenz, MD) P50 AG008702 (PI Scott Small, MD), P50 AG025688 (PI Allan Levey, MD, PhD), P50 AG047266 (PI Todd Golde, MD, PhD), P30 AG010133 (PI Andrew Saykin, PsyD), P50 AG005146 (PI Marilyn Albert, PhD), P30 AG062421-01 (PI Bradley Hyman, MD, PhD), P30 AG062422-01 (PI Ronald Petersen, MD, PhD), P50 AG005138 (PI Mary Sano, PhD), P30 AG008051 (PI Thomas Wisniewski, MD), P30 AG013854 (PI Robert Vassar, PhD), P30 AG008017 (PI Jeffrey Kaye, MD), P30 AG010161 (PI David Bennett, MD), P50 AG047366 (PI Victor Henderson, MD, MS), P30 AG010129 (PI Charles DeCarli, MD), P50 AG016573 (PI Frank LaFerla, PhD), P30 AG062429-01(PI James Brewer, MD, PhD), P50 AG023501 (PI Bruce Miller, MD), P30 AG035982 (PI Russell Swerdlow, MD), P30 AG028383 (PI Linda Van Eldik, PhD), P30 AG053760 (PI Henry Paulson, MD, PhD), P30 AG010124 (PI John Trojanowski, MD, PhD), P50 AG005133 (PI Oscar Lopez, MD), P50 AG005142 (PI Helena Chui, MD), P30 AG012300 (PI Roger Rosenberg, MD), P30 AG049638 (PI Suzanne Craft, PhD), P50 AG005136 (PI Thomas Grabowski, MD), P30 AG062715-01 (PI Sanjay Asthana, MD, FRCP), P50 AG005681 (PI John Morris, MD), P50 AG047270 (PI Stephen Strittmatter, MD, PhD).

For use with the ADGC-TARCC-WGS (snd10030) data:

This study was made possible by the Texas Alzheimer’s Research and Care Consortium (TARCC) funded by the state of Texas through the Texas Council on Alzheimer’s Disease and Related Disorders and the Darrell K Royal Texas Alzheimer’s Initiative.

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