☆ 4.0 Article

Comprehensive Search for Alzheimer Disease Susceptibility Loci in the APOE Region

ARCHIVES OF NEUROLOGY (2012)

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Journal

ARCHIVES OF NEUROLOGY
Volume 69, Issue 10, Pages 1270-1279

Publisher

AMER MEDICAL ASSOC
DOI: 10.1001/archneurol.2012.2052

Keywords

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Categories

Clinical Neurology

Funding

  1. GlaxoSmithKline
  2. Kronos Science
  3. Northern California Institute for Research and Education
  4. Abbott
  5. AstraZeneca AB
  6. Bayer Schering Pharma AG
  7. Bristol-Myers Squibb
  8. Eisai Global Clinical Development
  9. Elan Corporation
  10. Genentech
  11. GE Healthcare
  12. Innogenetics
  13. Johnson Johnson
  14. Eli Lilly and Co
  15. Medpace Inc
  16. Merck and Co Inc
  17. Novartis AG
  18. Pfizer Inc
  19. F. Hoffman-La Roche
  20. Schering-Plough
  21. Synarc Inc.
  22. National Institutes of Health NIA
  23. National Institutes of Health NIA through ADGC [U01 AG032984, RC2 AG036528]
  24. National Institutes of Health NIA through National Alzheimer's Coordinating Center [U01 AG016976]
  25. National Institutes of Health NIA through National Cell Repository for Alzheimer's Disease [U24 AG021886]
  26. National Institutes of Health NIA through NIA Late-Onset Alzheimer's Disease Study [U24 AG026395, U24 AG026390]
  27. National Institutes of Health NIA through Banner Sun Health Research Institute [P30 AG019610]
  28. National Institutes of Health NIA through Boston University [P30 AG013846, U01 AG10483, R01 CA129769, R01 MH080295, R01 AG017173, R01 AG025259, R01 AG33193]
  29. National Institutes of Health NIA through Columbia University [P50 AG008702, R37 AG015473]
  30. National Institutes of Health NIA through Duke University [P30 AG028377, R01 AG05128, R01 NS39764, R01 MH60451]
  31. National Institutes of Health NIA through Emory University [AG025688]
  32. National Institutes of Health NIA through Group Health Research Institute [UO1 AG06781, UO1 HG004610]
  33. National Institutes of Health NIA through Indiana University [P30 AG10133]
  34. National Institutes of Health NIA through Johns Hopkins University [P50 AG005146, R01 AG020688]
  35. National Institutes of Health NIA through Massachusetts General Hospital [P50 AG005134]
  36. National Institutes of Health NIA through Mayo Clinic [P50 AG016574]
  37. National Institutes of Health NIA through Mount Sinai School of Medicine [P50 AG005138, P01 AG002219]
  38. National Institutes of Health NIA through New York University [P30 AG08051, MO1 RR00096, UL1 RR029893]
  39. National Institutes of Health NIA through Northwestern University [P30 AG013854]
  40. National Institutes of Health NIA through Oregon Health & Science University [P30 AG008017, R01 AG026916]
  41. National Institutes of Health NIA through Rush University [P30 AG010161, R01 AG019085, R01 AG15819, R01 AG17917, R01 AG30146]
  42. National Institutes of Health NIA through Translational Genomics Research Institute [R01 NS059873, R01 AG034504]
  43. National Institutes of Health NIA through University of Alabama at Birmingham [P50 AG016582, UL1 RR02777]
  44. National Institutes of Health NIA through University of Arizona [R01 AG031581]
  45. National Institutes of Health NIA through University of California, Davis [P30 AG010129]
  46. National Institutes of Health NIA through University of California, Irvine [P50 AG016573, P50 AG016575, P50 AG016576, P50 AG016577]
  47. National Institutes of Health NIA through University of California, Los Angeles [P50 AG016570]
  48. National Institutes of Health NIA through University of California, San Diego [P50 AG005131]
  49. National Institutes of Health NIA through University of California, San Francisco [P50 AG023501, P01 AG019724]
  50. National Institutes of Health NIA through University of Kentucky [P30 AG028383, AG05144]
  51. National Institutes of Health NIA through University of Michigan [P50 AG008671]
  52. National Institutes of Health NIA through University of Pennsylvania [P30 AG010124]
  53. National Institutes of Health NIA through University of Pittsburgh [P50 AG005133, AG030653]
  54. National Institutes of Health NIA through University of Southern California [P50 AG005142]
  55. National Institutes of Health NIA through University of Texas Southwestern [P30 AG012300]
  56. National Institutes of Health NIA through University of Miami [R01 AG027944, AG010491, AG027944, AG021547, AG019757]
  57. National Institutes of Health NIA through University of Washington [P50 AG005136]
  58. National Institutes of Health NIA through Vanderbilt University [R01 AG019085]
  59. National Institutes of Health NIA through Washington University [P50 AG005681, P01 AG03991]
  60. NIA [U24 AG21886, U01 AG024904, RC2 AG036535, K01 AG030514]
  61. Banner Alzheimer's Foundation
  62. Johnnie B. Byrd Sr Alzheimer's Center & Research Institute
  63. Medical Research Council
  64. state of Arizona
  65. local National Health Service trusts
  66. Newcastle University
  67. Higher Education Funding Council for England
  68. Alzheimer's Research Trust
  69. BRACE
  70. North Bristol NHS Trust Research and Innovation Department
  71. DeNDRoN
  72. Stichting MS Research
  73. BrainNet Europe
  74. Hersenstichting Nederland Breinbrekend Werk
  75. International Parkinson Fonds
  76. Internationale Stiching Alzheimer Onderzoek
  77. Alzheimer's Association
  78. Alzheimer's Drug Discovery Foundation
  79. Dana Foundation
  80. National Institute of Biomedical Imaging and Bioengineering
  81. Alzheimer's Association [IIRG-08-89720, IIRG-05-14147]
  82. US Department of Veterans Affairs Administration
  83. Office of Research and Development
  84. Biomedical Laboratory Research Program
  85. Wellcome Trust
  86. Howard Hughes Medical Institute
  87. 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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