期刊
ALZHEIMERS & DEMENTIA
卷 11, 期 12, 页码 1439-1451出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jalz.2015.05.015
关键词
Obesity; Dementia; Alzheimer's disease; Mendelian randomization
资金
- NINDS [NS39764]
- NIMH [MH60451]
- GlaxoSmithKline
- Kronos Science
- NIA [AG041232]
- Medical Research Council
- local NHS trusts
- Newcastle University
- Higher Education Funding Council for England (HEFCE)
- Alzheimer's Research Trust (ART)
- BRACE
- North Bristol NHS Trust Research and Innovation Department and DeNDRoN
- Brain Net Europe
- Hersenstichting Nederland Breinbrekend Werk
- International Parkinson Fonds
- Internationale Stiching Alzheimer Onder-zoek
- National Institutes of Health [U01 AG024904]
- DOD ADNI [W81XWH-12-2-0012]
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- AbbVie
- Alzheimer's Association [IIRG-08-89720, IIRG-05-14147]
- Alzheimer's Drug Discovery Foundation
- Araclon Biotech
- BioClinica, Inc.
- Biogen
- Bristol-Myers Squibb Company
- CereSpir, Inc.
- Eisai Inc.
- Elan Pharmaceuticals, Inc.
- Eli Lilly and Company
- EuroImmun
- F. Hoffmann-La Roche Ltd
- Genentech, Inc.
- Fujirebio
- GE Healthcare
- IXICO Ltd.
- Janssen Alzheimer Immunotherapy Research & Development, LLC.
- Johnson & Johnson Pharmaceutical Research & Development LLC.
- Lumosity
- Lundbeck
- Merck Co., Inc.
- Meso Scale Diagnostics, LLC.
- NeuroRx Research
- Neurotrack Technologies
- Novartis Pharmaceuticals Corporation
- Pfizer Inc.
- Piramal Imaging
- Servier
- Takeda Pharmaceutical Company
- Transition Therapeutics
- Canadian Institutes of Health Research
- Northern California Institute for Research and Education
- US Department of Veterans Affairs Administration, Office of Research and Development, Biomedical Laboratory Research Program
- Wellcome Trust
- Howard Hughes Medical Institute
- Canadian Institute of Health Research
- National Institutes of Health, National Institute on Aging (NIH-NIA): ADGC [U01 AG032984, RC2 AG036528]
- National Institutes of Health, National Institute on Aging (NIH-NIA): NACC [U01 AG016976]
- National Institutes of Health, National Institute on Aging (NIH-NIA): NCRAD [U24 AG021886]
- National Institutes of Health, National Institute on Aging (NIH-NIA): NIA LOAD [U24 AG026395, U24 AG026390]
- National Institutes of Health, National Institute on Aging (NIH-NIA): Banner Sun Health Research Institute [P30 AG019610]
- National Institutes of Health, National Institute on Aging (NIH-NIA): Boston University [P30 AG013846, U01 AG10483, R01 CA129769, R01 MH080295, R01 AG017173, R01 AG025259, R01 AG33193]
- National Institutes of Health, National Institute on Aging (NIH-NIA): Columbia University [P50 AG008702, R37 AG015473]
- National Institutes of Health, National Institute on Aging (NIH-NIA): Duke University [P30 AG028377, AG05128]
- National Institutes of Health, National Institute on Aging (NIH-NIA): Emory University [AG025688]
- National Institutes of Health, National Institute on Aging (NIH-NIA): Group Health Research Institute [U01 AG06781, U01 HG004610, U01 HG006375]
- National Institutes of Health, National Institute on Aging (NIH-NIA): Indiana University [P30 AG10133]
- National Institutes of Health, National Institute on Aging (NIH-NIA): Johns Hopkins University [P50 AG005146, R01 AG020688]
- National Institutes of Health, National Institute on Aging (NIH-NIA): Massachusetts General Hospital [P50 AG005134]
- National Institutes of Health, National Institute on Aging (NIH-NIA): Mayo Clinic [P50 AG016574]
- National Institutes of Health, National Institute on Aging (NIH-NIA): Mount Sinai School of Medicine [P50 AG005138, P01 AG002219]
- National Institutes of Health, National Institute on Aging (NIH-NIA): New York University [P30 AG08051, MO1RR00096, UL1 RR029893, 5R01AG012101, 5R01AG022374, 5R01AG013616, 1RC2AG036502, 1R01 AG035137]
- National Institutes of Health, National Institute on Aging (NIH-NIA): Northwestern University [P30 AG013854]
- National Institutes of Health, National Institute on Aging (NIH-NIA): Oregon Health & Science University [P30 AG008017, R01 AG026916]
- National Institutes of Health, National Institute on Aging (NIH-NIA): Rush University [P30 AG010161, R01 AG019085, R01 AG15819, R01 AG17917, R01 AG30146]
- National Institutes of Health, National Institute on Aging (NIH-NIA): TGen [R01 NS059873]
- National Institutes of Health, National Institute on Aging (NIH-NIA): University of Alabama at Birmingham [P50 AG016582, UL1RR02777]
- National Institutes of Health, National Institute on Aging (NIH-NIA): University of Arizona [R01 AG031581]
- National Institutes of Health, National Institute on Aging (NIH-NIA): University of California, Davis [P30 AG010129]
- National Institutes of Health, National Institute on Aging (NIH-NIA): University of California, Irvine [P50 AG016573, P50, P50 AG016575, P50 AG016576, P50 AG016577]
- National Institutes of Health, National Institute on Aging (NIH-NIA): University of California, Los Angeles [P50 AG016570]
- National Institutes of Health, National Institute on Aging (NIH-NIA): University of California, San Diego [P50 AG005131]
- National Institutes of Health, National Institute on Aging (NIH-NIA): University of California, San Francisco [P50 AG023501, P01 AG019724]
- National Institutes of Health, National Institute on Aging (NIH-NIA): University of Kentucky [P30 AG028383, AG05144]
- National Institutes of Health, National Institute on Aging (NIH-NIA): University of Michigan [P50 AG008671]
- National Institutes of Health, National Institute on Aging (NIH-NIA): University of Pennsylvania [P30 AG010124]
- National Institutes of Health, National Institute on Aging (NIH-NIA): University of Pittsburgh [P50 AG005133, AG030653, AG041718]
- National Institutes of Health, National Institute on Aging (NIH-NIA): University of Southern California [P50 AG005142]
- National Institutes of Health, National Institute on Aging (NIH-NIA): University of Texas Southwestern [P30 AG012300]
- National Institutes of Health, National Institute on Aging (NIH-NIA): University of Miami [R01 AG027944, AG010491, AG027944, AG021547, AG019757]
- National Institutes of Health, National Institute on Aging (NIH-NIA): University of Washington [P50 AG005136]
- National Institutes of Health, National Institute on Aging (NIH-NIA): Vanderbilt University [R01 AG019085]
- National Institutes of Health, National Institute on Aging (NIH-NIA): Washington University [P50 AG005681, P01 AG03991]
Observational research shows that higher body mass index (BMI) increases Alzheimer's disease (AD) risk, but it is unclear whether this association is causal. We applied genetic variants that predict BMI in Mendelian randomization analyses, an approach that is not biased by reverse causation or confounding, to evaluate whether higher BMI increases AD risk. We evaluated individual-level data from the AD Genetics Consortium (ADGC: 10,079 AD cases and 9613 controls), the Health and Retirement Study (HRS: 8403 participants with algorithm-predicted dementia status), and published associations from the Genetic and Environmental Risk for AD consortium (GERAD1: 3177 AD cases and 7277 controls). No evidence from individual single-nucleotide polymorphisms or polygenic scores indicated BMI increased AD risk. Mendelian randomization effect estimates per BMI point (95% confidence intervals) were as follows: ADGC, odds ratio (OR) 5 0.95 (0.90-1.01); HRS, OR 5 1.00 (0.75-1.32); GERAD1, OR 5 0.96 (0.87-1.07). One subscore (cellular processes not otherwise specified) unexpectedly predicted lower AD risk. (C) 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
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