The Alzheimer's Disease Sequencing Project: Study design and sample selection
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Article Information
- Received May 1, 2017
- Accepted in final form August 17, 2017
- First Published October 13, 2017.
Author Disclosures
- Gary W. Beecham, PhD,
- J.C. Bis, PhD,
- E.R. Martin, PhD,
- S.-H. Choi, PhD,
- A. L. DeStefano, PhD,
- C.M. van Duijn, PhD,
- M. Fornage, PhD,
- S.B. Gabriel, PhD,
- D.C. Koboldt, PhD,
- D.E. Larson, PhD,
- A.C. Naj, PhD,
- B.M. Psaty, PhD,
- W. Salerno, PhD,
- W.S. Bush, PhD,
- T.M. Foroud, PhD,
- E. Wijsman, PhD,
- L.A. Farrer, PhD,
- A. Goate, PhD,
- J.L. Haines, PhD,
- Margaret A. Pericak-Vance, PhD,
- E. Boerwinkle, PhD,
- R. Mayeux, MD,
- S. Seshadri, MD and
- G. Schellenberg, PhD
- Gary W. Beecham, PhD,
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Dr. Beecham receives funding from the National Institutes of Health (R21HD080410, co-investigator, 2016-18; R01AG054080, PI, 2016-21; R01AG054074, MPI, 2016-21; U54AG052427, co-investigator, 2016-21; U01AG052410, MPI, 2016-21; U54NS0657, co-investigator, 2009-19; R01AG042437, subcontract PI, 2014-18; UF1AG047133, co-investigator, 2014-18; T32EY023194, co-investigator, 2013-2017; P50NS071674, co-investigator, 2010-17;U01G032984, co- investigator, 2009-2020; R01NS075764, co-investigator, 2012-17; R01AG027944, coinvestigator, 2008-2015) and the Department of Defense (W81XWH-14-1-0097, co-investigator, 2014-18).
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- J.C. Bis, PhD,
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- E.R. Martin, PhD,
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Frontiers in Statistical Genetics and Methodology, Associate Editor, Nov. 2010 - present
Invrntor, US Patenet No. 6697739 Test for Linkage and Association in General Pedigrees: The Pedigree Disequilibrium Test
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- S.-H. Choi, PhD,
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- A. L. DeStefano, PhD,
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1. NIH/NIDDK R01 DK099269, PI, 07/01/14-06/30/18 2. NIH/NHLBI HHSN268201500001, Statistical Geneticist 02/01/02-03/31/20 3. NIH/NIA 5 R01 AG033193-04, Co-investigator 07/01/13-06/30/17 4. NIH/NIA U01 AG049505-01 Co-investigator 02/01/13-01/31/17 5. NIH/NIA R01 AG054076-01 Statistical Geneticist 09/01/16 - 05/31/21
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- C.M. van Duijn, PhD,
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- M. Fornage, PhD,
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- S.B. Gabriel, PhD,
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I work for a non-profit entity
Wilmer-Hale Guidepoint Global
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- D.C. Koboldt, PhD,
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I receive a co-inventor's share of license revenue for VarScan, a software tool for next-generation sequencing analysis. Licensing and disbursements are handled by my former institution, Washington University in St. Louis. In the past two years, paying licensees included:(1) Bina Technologies (2) Janssen (3) Fera Science (4) Philips Electronics (5) WuXi NextCODE
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- D.E. Larson, PhD,
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(1) NIH, 1U41HG007635, Bioinformatician/Analysis, 2013-2016 (2) NIH, 1UM1HG008853, Bioinformatician/Analysis, 2016-2017 (3) NIH, 5R01CA178397, Bioinformatician/Analysis, 2015 (4) NIH, 5U01HG006517, Bioinformatician/Analysis, 2013-2016 (5) NIH, 5U54HG003079, Bioinformatician/Analysis, 2013-2015 (6) St. Jude Children's Research Hospital, Pediatric Cancer Genome Project Phase II, Bioinformatician/Analysis, 2013-2016
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- A.C. Naj, PhD,
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(1) Pfizer, presentation of a scientific talk
(1) Associate Editor, PLoS ONE
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(1) NIA, R01 AG054060, PI, 10/2016-9/2020 (2) NIA, U54 NS100693, Co-I, 9/2016-6/2020 (3) NIA, U54 AG052427, Co-I, 7/2016-6/2018 (4) NIA, U01 AG032984, Co-I, 6/2015-3/2020 (5) NIA, U24 AG041689, Co-I, 4/2015-3/2017 (6) NIA, R01 AG042437, Co-I, 9/2014-6/2018 (7) NIA, UF1 AG047133, Co-I, 6/2014-5/2018
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(1) BrightFocus Foundation, Co-I, 7/2016-6/2018 (2) Penn Institute on Aging, PI, 7/2016-6/2017
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- B.M. Psaty, PhD,
Psaty serves on the DSMB of a clinical trial for a device funded by the manufacturer (Zoll LifeCor) and on the Steering Committee for the Yale Open Data Access project funded by Johnson & Johnson.
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Contributing writer for JAMA.
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Listed in the acknowledgement
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- W. Salerno, PhD,
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LaserGen
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- W.S. Bush, PhD,
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BMC Biodata Mining, Editorial Board Member, 2012 - Present PLoS One, Statistical Advisory Board, 2013 - Present
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LaserGen
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NIA, AG054074, Co-I, 2016-Present NIA, AG052410, Co-I, 2016-Present NIA, AG052426, Co-I, 2016-Present
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- T.M. Foroud, PhD,
1) National Advisory Council on Alcohol Abuse and Alcoholism 2) Washington University Alzheimer?s Disease Research Center External Advisory Board3) NIA Genetics of Alzheimer's Disease Data Storage Site, External Advisory Board
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1) Michael J Fox Foundation for Parkinson's Research, travel 2) NIH, travel 3) Univ of Pittsburgh, travel 4) Univ of Chicago, travel 5) Univ of Texas at Austin, travel & speaker honoraria
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LaserGen
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1) NIH, PI or Co-I, 1997-2017 2) US Dept of Defense, W81XWH-14-2-0151, 2016-2017
1) Columbia Univ 2) San Diego State University 3) Univ Calif San Diego 4) Univ of Mass 5) Univ of Pennsylvania 6) State Univ of New York
Michael J Fox Foundation for Parkinson's Research
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- E. Wijsman, PhD,
Non-profit entity: NIH NHLBI National Registry for Genetically Triggered Thoracic Aortic Aneurisms and Cardiovascular Conditions, DSMB, 2007-2015
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BMC Proceedings, Editor, 2014-2016 Faculty of 1000, Editor, Bioinformatics section, 2013-present
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US National Institutes of Health: P30 AG05136, PI, Data Management/Biostatistics Core, 2005-current R37 GM46255, Co-I, 2008-current R01 MH094293, PI, 2012-current U01 AG049507, PI, 2014-current R24 OD021324, site PI, 2016-current R21 AI127493, PI, 2016-current R21 AI119715, PI, 2015-current
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Metropolitan Life Foundation Award for Medical Research
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- L.A. Farrer, PhD,
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1. American Journal of Alzheimer's Disease & Other Dementias, editorial board, 1997-present 2. Clinical Genetics, editorial board, 1999-present
one patent pending for use of PLXNA4 as a drug target and biomarker for Alzheimer disease
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1. Novartis Pharmaceuticals, consultant, 2007-2010 2. Gerson Lerman, consultant, 2009-present 3. Guidepoint Global, 2009 - present
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NIH - R01-AG25259, PI, 2006-2112 NIH - U01-AG032984, SubK PI, 2009-present NIH - UF1-AG046198, PI of a multi PI grant, 2014-present NIH - R01-AG048927, PI, 2015-present
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Fidelity Foundation, research grant (PI), 2007-2011 Thome Memorial Foundation, research grant (PI), 2012-2014
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Finnegan & Associates, LLP, consultant, 2011
- A. Goate, PhD,
(1) Denali Therapeutics
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Rainwater Foundation 2014-2016 travel to attend meeting Indiana University ADRC advisory board 2015, 2016
eLife, reviewing editor
PSEN mutations in AD Tau mutations in FTD TDP43 mutations in ALS\FTD
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Cognition Therapeutics 2015 AbbVie 2016
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F Prime
1. NIA 1R01AG035083- (Goate) PI 9/1/10-8/31/15 2. NIA 1U01AG032984-01 (Schellenberg\Goate) Co- Investigator/Core Director 4/1/09-3/31/14 3. NIA U01 AG049508-01 Goate (PI) 6/11/14-5/31/18 4. NIA R01 AGO41797-03 Goate Site PI 4/1/12-3/13/17 5. NIA U01 AG052411 Goate (PI) 8/1/2016-7/31/2020 6. NIA RF1AG05401 Goate (PI) 08/01/16-06/30/21 7. NIA 5U01AG032438-07 (Morris) Co-Investigator/Core Director 9/15/08-6/30/19 8. NIAAA 5U10AA08401-25 (Goate/ site PI) Co-Investigator 9/29/89-8/31/19
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1. Rainwater Charitable Foundation 2. JPB Foundation
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Taconic Industries for tau mutation patent
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- J.L. Haines, PhD,
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1). Neurogenetics, editorial board member, 2006-present 2). Current Protocols in Human Genetics, editorial board member, 1993-present 3). Human Molecular Genetics, editorial board member 2014-present
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1). Current protocols in Human Genetics, John Wiley &Sons, 1994-present
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2014/06/15-2018/05/31 UF1AG047133, NIH/NIA Consortium for Alzheimer?s Sequence Analysis (CASA) The goal of the CASA grant is to analyze and interpret genotyping and sequencing data from a large dataset of Alzheimer cases, controls, and families Role: KP (PI)2013/02/01-2018/01/31 R01EY023164, NIH/NEI Stambolian (U. Penn) (PI) Genetic Epidemiology of Age-Related Macular Degeneration in the Old Order Amish The goal of this project is to understand the genetic architecture of AMD phenotypes in the Amish Role: KP (PI of subcontract)2011/09/01-2016/08/31 R01EY020928, NIH/NEI Wiggs (Mass. Eye & Ear) (PI) Genetic and Environmental Risk Factors for Exfoliation Syndrome and Glaucoma The goal of this project is to generate GWAS data on glaucoma patients and examine the results for both gene and gene environment effects. Role: KP (PI of subcontract)2000/06/15-2016/07/31 R01EY012118, NIH/NEI Haines, Jonathan L. (PI) Genomic Architecture of Progression and Treatment Response in AMD The goal of this project is to dissect the genetic etiology of Macular Degeneration Role: PI2012/04/01-2016/03/31 R01EY022310, NIH/NEI Haines, Jonathan L. (PI) Advancing Genetics through the AMD Gene Consortium The goal of this project is to combine data and results from multiple different investigators to further understand the genetic architecture of age-related macular degeneration Role: PI2012/08/01-2019/07/31 R01EY022305, NIH/NEI Wiggs (Mass. Eye & Ear) (PI) The NEIGHBORHOOD: POAG Heritable Overall Operational Database The goal of this project is to combine data and results from multiple different investigators to further understand the genetic architecture of Primary Open AngleGlaucoma. Role: KP (PI of subcontract)
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- Margaret A. Pericak-Vance, PhD,
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1. Genetic Epidemiology, Editor, 2006-present 2. Molecular Autism, Editor, 2008-present 3. Molecular Autism Editorial Board, Member, 2010-present 4. Advances in Genomics and Gene Expression Editorial Board, Member, 2010-present Immediate Family Member: Dr. Jeffery Vance 1. Neurology Genetics, Associate Editor, 2015-present 2. Editorial Board of American Journal of Neurodegenerative Disease, 2012-present
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1. NIH, AG054080, Co-I, 2016 to 2021. 2. NIH-NIA, AG054074, PI, 2016-2021. 3. NIH-NIA, AG052410, PI, 2016-2021. 4. NIH-NIMHD, MD010722, subcontract PI, 2016 to 2021. 5. NIH-NIA, AG052427, subcontract PI, 2016-2021. 6. NIH, AG047133, PI, 2014-2018. 7. NIH-NIA, AG032984, subcontract PI, 2009-2020. 8. NIH-NEI, EY023164, PI, 2013-2018. 9. NIH, EY022310, PI, 2012-2018. 10. DOD, W81XWH-12-1-0013, PI, 2012-2017. 11. NIH-NEI, EY012118, PI, 2011-2017.
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1. JJ Vance Foundation
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- E. Boerwinkle, PhD,
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American Society for Bone and Mineral Research, honorarium for speaking.
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Scientific Officer at Codified Genomics, LLC.
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5U01HG007416-03 (North) NIH/NHGRI Univ. of NC at Chapel Hill 09/01/2013 - 05/31/2018 Genetic Epidemiology of Causal Variants Across the Life Course Phase 2 (CALiCo 2) CALiCo is an ethnically diverse consortium of population based studies that investigate the genetic architecture of variants associated with complex diseases. Role: Consortium PI 5U01AG049506-03 (Boerwinkle) NIH/NIA 06/15/2014 - 05/31/2018 Sequence-based Discovery of AD Risk & Protective Alleles This project seeks to identify genes from whole genome sequence data associated with increased risk of or protection from Alzheimer's Disease. Role: PI 5R01NS087541-03 (Fornage/Boerwinkle) NIH/NINDS 04/01/2014 - 03/31/2018 An Integrated Genetic and Epigenetic Approach to Cerebral Small Vessel Disease This study aims to identify epigenetic variation (DNA methylation) influencing cerebral small vessel disease. Role: Multi-PI 1UM1HG008898-01 (Gibbs) NIH/NHGRI Baylor College of Medicine 11/01/2015 ?10/31/2019 Genomic Architecture of Common Disease in Diverse Populations In this project, whole genome sequencing will be performed to identify genomic regions influencing the human serum metabolome. Role: Consortium PI 5UL1TR000371-09 (McPherson) NIH/NCATS 06/27/2012 - 05/31/2018 Center for Clinical and Translational Sciences The goal of the Center for Clinical and Translational Sciences (CCTS) is to facilitate clinical and translational research at The University of Texas Health Science Center at Houston, The University of Texas M.D. Anderson Cancer Center, and the Memorial Hermann Hospital System. Role: Co-Investigator HHSN268201700001I (Couper) NIH/NHLBI Univ. of NC at Chapel Hill 11/15/2016-11/14/2022 Atherosclerosis Risk in Communities (ARIC) Study This project maintains longitudinal samples collected as part of the well-established NHLBI ARIC study and analyzes large scale genomic data and gene-environment interactions of cardiovascular disease related phenotypes and risk factors. Role: Consortium PI 5R01HL120393-03 (Psaty) NIH/NHLBI Univ. of Washington Rare Variants and NHLBI Traits in Deeply Phenotyped Cohorts 04/01/2014 - 03/31/2018 This research investigates the impact of rare variants in heart, lung and blood phenotypes in a consortium of large population-based cohorts, such as the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Role: Consortium PI 1R01DK101505-02 (Kelly) NIH/NIDDK Tulane University 08/21/2015 ? 05/31/2020 Whole-exome Sequencing Study of Diabetic Nephropathy This study proposes to identify novel genes and functional variants associated with diabetic nephropathy (DN) by conducting whole-exome sequencing, follow-up targeted sequencing, and replication in a multiethnic cohort. Role: Co-Investigator 2R01HL105756-04 (Psaty) NIH/NHLBI U of Washington 03/01/2014 ? 03/31/2018 Charge Consortium: Gene Discovery for CVD and Aging Phenotypes We will perform statistical analysis of cardiovascular disease and related aging phenotypes in ARIC genetic data as part of the CHARGE consortium. Role: Consortium PI 1U01HG008664-01 (Gibbs) NIH/NHGRI Baylor College of Medicine 09/01/2015 ? 05/31/2019 DNA Sequencing Support for the eMERGE Network Annotation will be customized and revalidated for whole genome sequence data collected as part of the eMERGE program. Role: Consortium PI 1R01HL131136-01A1 (Boerwinkle) NIH/NHLBI 12/15/2016 ? 11/30/2020 Epigenetics of Successful Aging This project will test the hypothesis that DNA methylation signatures measured in the blood of middle-adults are associated with successful aging patterns later in life. Role: PI UM1HG006542 (Valle) NIH/NHGRI Johns Hopkins University 12/05/2011 ? 11/30/2019 Baylor-Johns Hopkins Center for Mendelian Genetics This project analyzes sequence data to identify genes leading to targeted Mendelian disorders. Role: Co-Investigator 4R01GM104411-04 (Xiong) NIH/NIGMS 04/01/2013 - 01/31/2018 Unified Statistical Methods for Sequence-Based Association Studies This project develops and tests innovative genetic models, statistical methods and computational algorithms for sequence-based association studies and QTL analysis. Role: Multi-PI
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- R. Mayeux, MD,
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RO1 AG037212 Epidemiology of Biomarkers of Risk and Progression in Late onset Alzheimer?s Disease. Principal Investigator RF1 AG015473 Genetic Studies of Alzheimer's Disease in Caribbean Hispanics. Principle Investigator
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- S. Seshadri, MD and
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Journal of Alzheimer's Disease, Associate Editor since 2005. Stroke: Editorial Board since 2010. Neurology: Editorial Board since 2011.
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NIA AG008122, AG033040, AG049505, AG033193, AG049607, AG054076
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- G. Schellenberg, PhD
Alzheimer's Association Medical Advisory Board, Society of Progressive Supranuclear Palsy Scientific Advisory Board, Alzheimer Research Consortium Peebler PSP Research Foundation Medical and Scientific Advisory Committee - Alzheimer's Association External Scientific Advisory Board, United Kingdom Parkinson Disease Center, University College London Member, Steering Committee, Alzheimer?s Disease Sequence Project Co-chair, Structural Variant Work Group, Alzheimer?s Disease Sequence Project 2013-present External Advisory Committee, Mayo Clinic Rochester Udall center External Advisory Committee, University of Miami Udall Center Member, External Advisor ? Discovery Assessment Panel, Oxford Parkinson?s Disease Centre
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Alzheimer's Disease Center Directors Meeting - travel/lodging CurePSP International Research Symposium, travel/lodging Robert Katzman Memorial Lecture, University of California, San Diego, California Alzheimer?s Disease ? From Fundamental Insights to Light at the End of the Translational Tunnel, Keystone, Colorado 25th Annual Southern California Alzheimer?s Disease Research Conference, University of California Institute for Memory Impairment and Neurological Disorders, Costa Mesa, California CurePSP International Research Symposium, Baltimore, Maryland Biomarkers in Neuropsychiatric Disorders, Toronto, Canada Alzheimer?s Disease Sequence Project meeting, National Institutes of Health, Bethesda, Maryland Path to Treatment and Prevention, National Institutes of Health, Bethesda, Maryland Novartis Institutes for Biomedical Research, Inc., Novartis, Cambridge, Massachusetts McKnight Brain Institute, University of Florida, Gainesville, Florida Alzheimer?s Disease Center Directors Meeting, Washington, DC. NIA Scientific Retreat, National Institutes of Health, Bethesda, Maryland Keep Memory Alive Event Center, Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV Accelerated Medicines Program Alzheimer?s Disease F2F Target Discovery and Preclinical Validation Project Meeting. ?Alzheimer?s Disease Sequencing Project ? status?, NIA/FNIH/NIH, Bethesda, MD ?Genetics of PSP and Tauopathies?, PSP/Lewy Body Disease Think-Tank. Journey from Tau to Lewy bodies. McKnight Brain Institute, University of Florida, Gainesville, Florida ?ADGC Update, NIAGADS Update? Alzheimer?s Disease Center Directors Meeting, Washington, DC. ?Update on Alzheimer?s Disease Sequence Project?, 2015 NIA Scientific Retreat, National Institutes of Health, Bethesda, Maryland ?GWAS and ?Omics Implications for Combination Therapy,? Keep Memory Alive Event Center, Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV Accelerated Medicines Program Alzheimer?s Disease F2F Target Discovery and Preclinical Validation Project Meeting. ?Alzheimer?s Disease Sequencing Project ? status?, NIA/FNIH/NIH, Bethesda, MD American Association of Neuropathologists, ?Alzheimer?s Disease Genetics? Denver, CO. Fusion Conference, Personalized Medicine, ?Personalized Medicine and Neurodegenerative disorders. What does the future hold?? Tucson, AZ. CurePSP Symposium, ?Progressive supranuclear palsy genetics ? update?. La Jolla, CA Center for Public Health Genomics, Genome Sciences Seminar, University of Virginnia, ?Progress in Neurodegenerative Disease Genetics?, Charlottesville, VA. Neurology Grand Rounds, Columbia University, ?Genetics of Progressive supranuclear palsy and corticobasal degeneration?, New York, NY.
Advisory Board for the Dementia Section, Journal of Neural Transmission Editorial Board, Alzheimer's Research Editorial Board, American Journal of Alzheimer?s Disease and other Dementias. Editorial Board, Neurodegenerative Diseases Editorial Board, Current Alzheimer Research Editorial Board - Pathology and Laboratory Medicine International
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Professor - University of Pennsylvania
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NIA/NIH
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CurePSP CBD Solutions
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- From the John P. Hussman Institute for Human Genomics (G.W.B., E.R.M., M.A.P.-V.) and Dr. John T. Macdonald Foundation Department of Human Genetics (G.W.B., E.R.M., M.A.P.-V.), Miller School of Medicine, University of Miami, FL; Cardiovascular Health Research Unit (J.C.B.), Department of Medicine, Cardiovascular Health Research Unit (B.M.P.), Departments of Medicine, Epidemiology, Health Services, Department of Biostatistics (E.W.), and Division of Medical Genetics (E.W.), Department of Medicine, University of Washington, Seattle; Department of Biostatistics (S.-H.C., A.D., L.A.F.), Boston University School of Public Health, MA; The Framingham Heart Study (A.D., S.S.), MA; Department of Neurology (A.D., L.A.F., S.S.), Boston University School of Medicine, MA; Department of Epidemiology (C.M.v.D), Erasmus MC, Rotterdam, Netherlands; Brown Foundation Institute of Molecular Medicine (M.F.) and Human Genetics Center (M.F.), University of Texas Health Science Center, Houston; The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology (S.B.G.), Cambridge; Harvard University (S.B.G.), Cambridge, MA; The McDonnell Genome Institute (D.C.K., D.E.L.) and Department of Genetics (D.E.L.), Washington University, St. Louis, MO; Department of Biostatistics and Epidemiology (A.C.N.) and Perelman School of Medicine (G.S.), University of Pennsylvania, Philadelphia; Group Health Research Institute (B.M.P.), Group Health Cooperative, Seattle, WA; Human Genome Sequencing Center (W.S., E.B.), Baylor College of Medicine, Houston, TX; Department of Epidemiology and Biostatistics (W.S.B., J.L.H.), Case Western Reserve University, Cleveland, OH; Department of Medical and Molecular Genetics (T.M.F.), Indiana University School of Medicine, Indianapolis; Department of Medicine (Biomedical Genetics) (L.A.F.), Department of Ophthalmology (L.A.F.), and Department of Epidemiology (L.A.F.), Boston University School of Medicine and Public Health, MA; Department of Neuroscience (A.G.), Icahn School of Medicine at Mount Sinai, New York, NY; Human Genetics Center (E.B.), UT Health School of Public Health, Houston, TX; Taub Institute for Research on Alzheimer's Disease and the Aging Brain (R.M.) and Gertrude H. Sergievsky Center (R.M.), Columbia University Medical Center, New York, NY; Department of Neurology (R.M.), Columbia University Medical Center and New York Presbyterian Hospital, NY; and Department of Epidemiology (R.M.), Mailman School of Public Health, Columbia University, New York, NY.
- Correspondence to Dr. Beecham: gbeecham{at}med.miami.edu
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