Journal
ARCHIVES OF NEUROLOGY
Volume 69, Issue 10, Pages 1270-1279Publisher
AMER MEDICAL ASSOC
DOI: 10.1001/archneurol.2012.2052
Keywords
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Categories
Funding
- GlaxoSmithKline
- Kronos Science
- Northern California Institute for Research and Education
- Abbott
- AstraZeneca AB
- Bayer Schering Pharma AG
- Bristol-Myers Squibb
- Eisai Global Clinical Development
- Elan Corporation
- Genentech
- GE Healthcare
- Innogenetics
- Johnson Johnson
- Eli Lilly and Co
- Medpace Inc
- Merck and Co Inc
- Novartis AG
- Pfizer Inc
- F. Hoffman-La Roche
- Schering-Plough
- Synarc Inc.
- National Institutes of Health NIA
- National Institutes of Health NIA through ADGC [U01 AG032984, RC2 AG036528]
- National Institutes of Health NIA through National Alzheimer's Coordinating Center [U01 AG016976]
- National Institutes of Health NIA through National Cell Repository for Alzheimer's Disease [U24 AG021886]
- National Institutes of Health NIA through NIA Late-Onset Alzheimer's Disease Study [U24 AG026395, U24 AG026390]
- National Institutes of Health NIA through Banner Sun Health Research Institute [P30 AG019610]
- National Institutes of Health NIA through Boston University [P30 AG013846, U01 AG10483, R01 CA129769, R01 MH080295, R01 AG017173, R01 AG025259, R01 AG33193]
- National Institutes of Health NIA through Columbia University [P50 AG008702, R37 AG015473]
- National Institutes of Health NIA through Duke University [P30 AG028377, R01 AG05128, R01 NS39764, R01 MH60451]
- National Institutes of Health NIA through Emory University [AG025688]
- National Institutes of Health NIA through Group Health Research Institute [UO1 AG06781, UO1 HG004610]
- National Institutes of Health NIA through Indiana University [P30 AG10133]
- National Institutes of Health NIA through Johns Hopkins University [P50 AG005146, R01 AG020688]
- National Institutes of Health NIA through Massachusetts General Hospital [P50 AG005134]
- National Institutes of Health NIA through Mayo Clinic [P50 AG016574]
- National Institutes of Health NIA through Mount Sinai School of Medicine [P50 AG005138, P01 AG002219]
- National Institutes of Health NIA through New York University [P30 AG08051, MO1 RR00096, UL1 RR029893]
- National Institutes of Health NIA through Northwestern University [P30 AG013854]
- National Institutes of Health NIA through Oregon Health & Science University [P30 AG008017, R01 AG026916]
- National Institutes of Health NIA through Rush University [P30 AG010161, R01 AG019085, R01 AG15819, R01 AG17917, R01 AG30146]
- National Institutes of Health NIA through Translational Genomics Research Institute [R01 NS059873, R01 AG034504]
- National Institutes of Health NIA through University of Alabama at Birmingham [P50 AG016582, UL1 RR02777]
- National Institutes of Health NIA through University of Arizona [R01 AG031581]
- National Institutes of Health NIA through University of California, Davis [P30 AG010129]
- National Institutes of Health NIA through University of California, Irvine [P50 AG016573, P50 AG016575, P50 AG016576, P50 AG016577]
- National Institutes of Health NIA through University of California, Los Angeles [P50 AG016570]
- National Institutes of Health NIA through University of California, San Diego [P50 AG005131]
- National Institutes of Health NIA through University of California, San Francisco [P50 AG023501, P01 AG019724]
- National Institutes of Health NIA through University of Kentucky [P30 AG028383, AG05144]
- National Institutes of Health NIA through University of Michigan [P50 AG008671]
- National Institutes of Health NIA through University of Pennsylvania [P30 AG010124]
- National Institutes of Health NIA through University of Pittsburgh [P50 AG005133, AG030653]
- National Institutes of Health NIA through University of Southern California [P50 AG005142]
- National Institutes of Health NIA through University of Texas Southwestern [P30 AG012300]
- National Institutes of Health NIA through University of Miami [R01 AG027944, AG010491, AG027944, AG021547, AG019757]
- National Institutes of Health NIA through University of Washington [P50 AG005136]
- National Institutes of Health NIA through Vanderbilt University [R01 AG019085]
- National Institutes of Health NIA through Washington University [P50 AG005681, P01 AG03991]
- NIA [U24 AG21886, U01 AG024904, RC2 AG036535, K01 AG030514]
- Banner Alzheimer's Foundation
- Johnnie B. Byrd Sr Alzheimer's Center & Research Institute
- Medical Research Council
- state of Arizona
- local National Health Service trusts
- Newcastle University
- Higher Education Funding Council for England
- Alzheimer's Research Trust
- BRACE
- North Bristol NHS Trust Research and Innovation Department
- DeNDRoN
- Stichting MS Research
- BrainNet Europe
- Hersenstichting Nederland Breinbrekend Werk
- International Parkinson Fonds
- Internationale Stiching Alzheimer Onderzoek
- Alzheimer's Association
- Alzheimer's Drug Discovery Foundation
- Dana Foundation
- National Institute of Biomedical Imaging and Bioengineering
- Alzheimer's Association [IIRG-08-89720, IIRG-05-14147]
- 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
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Objective: To evaluate the association of risk and age at onset (AAO) of Alzheimer disease (AD) with single-nucleotide polymorphisms (SNPs) in the chromosome 19 region including apolipoprotein E (APOE) and a repeat-length polymorphism in TOMM40 (poly-T, rs10524523). Design: Conditional logistic regression models and survival analysis. Setting: Fifteen genome-wide association study data sets assembled by the Alzheimer's Disease Genetics Consortium. Participants: Eleven thousand eight hundred forty AD cases and 10 931 cognitively normal elderly controls. Main Outcome Measures: Association of AD risk and AAO with genotyped and imputed SNPs located in an 800-Mb region including APOE in the entire Alzheimer's Disease Genetics Consortium data set and with the TOMM40 poly-T marker genotyped in a subset of 1256 cases and 1605 controls. Results: In models adjusting for APOE epsilon 4, no SNPs in the entire region were significantly associated with AAO at P < .001. Rs10524523 was not significantly associated with AD or AAO in models adjusting for APOE genotype or within the subset of epsilon 3/epsilon 3 subjects. Conclusions: APOE alleles epsilon 2, epsilon 3, and epsilon 4 account for essentially all the inherited risk of AD associated with this region. Other variants including a poly-T track in TOMM40 are not independent risk or AAO loci.
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