Journal article

Whole-exome sequencing in 20,197 persons for rare variants in Alzheimer's disease

Neha S Raghavan, Adam M Brickman, Howard Andrews, Jennifer J Manly, Nicole Schupf, Rafael Lantigua, Charles J Wolock, Sitharthan Kamalakaran, Slave Petrovski, Giuseppe Tosto, Badri N Vardarajan, David B Goldstein, Richard Mayeux

Annals of Clinical and Translational Neurology | WILEY | Published : 2018

University of Melbourne Researchers

Grants

Awarded by National Institutes of Health (NIH)


Awarded by National Center for Advancing Translational Sciences, NIH


Awarded by NIA


Awarded by NHLBI


Awarded by National Heart, Lung, and Blood Institute (NHLBI)


Awarded by National Institute on Aging (NIA)


Awarded by National Alzheimer's Coordinating Center (NACC)


Awarded by National Institute on Aging Genetics of Alzheimer's Disease Data Storage Site (NIAGADS)


Awarded by National Institutes of Health


Awarded by National Institute of Neurological Disorders and Stroke


Awarded by National Institute of Child Health and Human Development


Awarded by National Institute of Mental Health


Awarded by National Human Genome Research Institute


Awarded by NIH Clinical and Translational Science Award Program


Awarded by Ellison Medical Foundation New Scholar award


Awarded by National Institute on Aging Late Onset Alzheimer's Disease Family Study (NIA-AD)


Awarded by Human Genome Sequencing Center at the Baylor College of Medicine


Awarded by Broad Institute Genome Center


Awarded by Washington University Genome Institute



Funding Acknowledgements

WHICAP and EFIGA: Data collection for this project was supported by the Washington Heights and Inwood Community Aging Project (WHICAP) and Genetic Studies of Alzheimer's disease in Caribbean Hispanics (Estudio familiar de la genetica de la enfermedad de Alzheimer, also known as EFIGA) funded by the National Institute on Aging (NIA), by the National Institutes of Health (NIH) (1RF1AG054023, 5R37AG015473, RF1AG015473, R56AG051876), and the National Center for Advancing Translational Sciences, NIH through Grant Number TL1TR001875. We acknowledge the WHICAP and EFIGA study participants and the research and support staff for their contributions to this study.ADSP; The Alzheimer's Disease Sequencing Project (ADSP) is comprised of two Alzheimer's Disease (AD) genetics consortia and three National Human Genome Research Institute (NHGRI) funded Large Scale Sequencing and Analysis Centers (LSAC). The two AD genetics consortia are the Alzheimer's Disease Genetics Consortium (ADGC) funded by NIA (U01 AG032984), and the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) funded by NIA (R01 AG033193), the National Heart, Lung, and Blood Institute (NHLBI), other National Institute of Health (NIH) institutes and other foreign governmental and nongovernmental organizations. The Discovery Phase analysis of sequence data is supported through UF1AG047133 (to Drs. Schellenberg, Farrer, Pericak-Vance, Mayeux, and Haines); U01AG049505 to Dr. Seshadri; U01AG049506 to Dr. Boerwinkle; U01AG049507 to Dr. Wijsman; and U01AG049508 to Dr. Goate and the Discovery Extension Phase analysis is supported through U01AG052411 to Dr. Goate and U01AG052410 to Dr. Pericak-Vance. Data generation and harmonization in the Follow-up Phases is supported by U54AG052427 (to Drs. Schellenberg and Wang).The ADGC cohorts include: Adult Changes in Thought (ACT), the Alzheimer's Disease Centers (ADC), the Chicago Health and Aging Project (CHAP), the Memory and Aging Project (MAP), Mayo Clinic (MAYO), Mayo Parkinson's Disease controls, University of Miami, the Multi-Institutional Research in Alzheimer's Genetic Epidemiology Study (MIRAGE), the National Cell Repository for Alzheimer's Disease (NCRAD), the National Institute on Aging Late Onset Alzheimer's Disease Family Study (NIA-AD; U24 AG056270), the Religious Orders Study (ROS), the Texas Alzheimer's Research and Care Consortium (TARC), Vanderbilt University/Case Western Reserve University (VAN/CWRU), the Washington Heights-Inwood Columbia Aging Project (WHICAP) and the Washington University Sequencing Project (WUSP), the Columbia University Hispanic-Estudio Familiar de Influencia Genetica de Alzheimer (EFIGA), the University of Toronto (UT), and Genetic Differences (GD).The CHARGE cohorts, with funding provided by 5RC2HL102419 and HL105756, include the following: Atherosclerosis Risk in Communities (ARIC) Study which is carried out as a collaborative study supported by NHLBI contracts (HHSN268201100005C, HHSN268-201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C), Austrian Stroke Prevention Study (ASPS), Cardiovascular Health Study (CHS), Erasmus Rucphen Family Study (ERF), Framingham Heart Study (FHS), and Rotterdam Study (RS). CHS research was supported by contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, and grants U01HL080295 and U01HL130114 from the National Heart, Lung, and Blood Institute (NHLBI), with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided by R01AG023629, R01AG15928, and R01AG20098 from the National Institute on Aging (NIA). A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.The three LSACs are: the Human Genome Sequencing Center at the Baylor College of Medicine (U54 HG003273), the Broad Institute Genome Center (U54HG003067), and the Washington University Genome Institute (U54HG003079).Biological samples and associated phenotypic data used in primary data analyses were stored at Study Investigators institutions, and at the National Cell Repository for Alzheimer's Disease (NCRAD, U24AG021886) at Indiana University funded by NIA. Associated Phenotypic Data used in primary and secondary data analyses were provided by Study Investigators, the NIA funded Alzheimer's Disease Centers (ADCs), and the National Alzheimer's Coordinating Center (NACC, U01AG016976) and the National Institute on Aging Genetics of Alzheimer's Disease Data Storage Site (NIAGADS, U24AG041689) at the University of Pennsylvania, funded by NIA, and at the Database for Genotypes and Phenotypes (dbGaP) funded by NIH. This research was supported in part by the Intramural Research Program of the National Institutes of health, National Library of Medicine. Contributors to the Genetic Analysis Data included Study Investigators on projects that were individually funded by NIA, and other NIH institutes, and by private U.S. organizations, or foreign governmental or nongovernmental organizations.The collection of control samples and data was funded in part by: Biogen; Gilead Sciences, Inc.; UCB; National Institutes of Health (RO1HD048805); National Institute of Neurological Disorders and Stroke (U01NS077303, U01NS053998, U54NS078059); National Institute of Child Health and Human Development (P01HD080642); National Institute of Mental Health (R01MH097971, K01MH098126); National Human Genome Research Institute (U01HG007672); an American Academy of Child and Adolescent Psychiatry (AACAP) Pilot Research Award; Endocrine Fellows Foundation Grant; the NIH Clinical and Translational Science Award Program (UL1TR000040); the Ellison Medical Foundation New Scholar award AG-NS-0441-08; Duke Chancellor's Discovery Program Research Fund 2014; The J. Willard and Alice S. Marriott Foundation; The Muscular Dystrophy Association; The Nicholas Nunno Foundation; The JDM Fund for Mitochondrial Research; The Arturo Estopinan TK2 Research Fund; the Stanley Institute for Cognitive Genomics at Cold Spring Harbor Laboratory; New York-Presbyterian Hospital; the Columbia University College of Physicians and Surgeons; and the Columbia University Medical Center.Biogen Inc. provided support for whole exome sequencing for the WHICAP cohort through a grant to David Goldstein, PhD and salary support for Neha S. Raghavan PhD for analyses. Individuals at Biogen were not involved in the collection of data, analysis or interpretation of the genetic data, nor in the production of this manuscript.