Comprehensive search for Alzheimer disease susceptibility loci in the APOE region.

TitleComprehensive search for Alzheimer disease susceptibility loci in the APOE region.
Publication TypeJournal Article
Year of Publication2012
AuthorsJun G, Vardarajan BN, Buros J, Yu C-E, Hawk MV, Dombroski BA, Crane PK, Larson EB, Mayeux R, Haines JL, Lunetta KL, Pericak-Vance MA, Gerard D Schellenberg, Farrer LA
Corporate AuthorsAlzheimer's Disease Genetics Consortium
JournalArch Neurol
Volume69
Issue10
Pagination1270-9
Date Published2012 Oct
ISSN1538-3687
KeywordsAge of Onset, Aged, Aged, 80 and over, Alzheimer Disease, Apolipoproteins E, Chromosomes, Human, Pair 19, Cohort Studies, DNA Repeat Expansion, Female, Gene Frequency, Genetic Association Studies, Genetic Predisposition to Disease, Genotype, Humans, Logistic Models, Male, Membrane Transport Proteins, Polymorphism, Single Nucleotide, Survival Analysis
Abstract

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 ε4, 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 ε3/ε3 subjects.CONCLUSIONS: APOE alleles ε2, ε3, and ε4 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.

DOI10.1001/archneurol.2012.2052
Alternate JournalArch. Neurol.
PubMed ID22869155
PubMed Central IDPMC3579659
Grant ListAG010491 / AG / NIA NIH HHS / United States
AG019757 / AG / NIA NIH HHS / United States
AG021547 / AG / NIA NIH HHS / United States
AG025688 / AG / NIA NIH HHS / United States
AG027944 / AG / NIA NIH HHS / United States
AG030653 / AG / NIA NIH HHS / United States
AG05144 / AG / NIA NIH HHS / United States
K01 AG030514 / AG / NIA NIH HHS / United States
M01 RR00096 / RR / NCRR NIH HHS / United States
P01 AG002219 / AG / NIA NIH HHS / United States
P01 AG019724 / AG / NIA NIH HHS / United States
P01 AG03991 / AG / NIA NIH HHS / United States
P30 AG008017 / AG / NIA NIH HHS / United States
P30 AG010124 / AG / NIA NIH HHS / United States
P30 AG010129 / AG / NIA NIH HHS / United States
P30 AG010161 / AG / NIA NIH HHS / United States
P30 AG012300 / AG / NIA NIH HHS / United States
P30 AG013846 / AG / NIA NIH HHS / United States
P30 AG013846 / AG / NIA NIH HHS / United States
P30 AG013854 / AG / NIA NIH HHS / United States
P30 AG019610 / AG / NIA NIH HHS / United States
P30 AG028377 / AG / NIA NIH HHS / United States
P30 AG028383 / AG / NIA NIH HHS / United States
P30 AG08051 / AG / NIA NIH HHS / United States
P30 AG10133 / AG / NIA NIH HHS / United States
P50 AG005131 / AG / NIA NIH HHS / United States
P50 AG005131 / AG / NIA NIH HHS / United States
P50 AG005133 / AG / NIA NIH HHS / United States
P50 AG005134 / AG / NIA NIH HHS / United States
P50 AG005136 / AG / NIA NIH HHS / United States
P50 AG005138 / AG / NIA NIH HHS / United States
P50 AG005142 / AG / NIA NIH HHS / United States
P50 AG005146 / AG / NIA NIH HHS / United States
P50 AG005681 / AG / NIA NIH HHS / United States
P50 AG008671 / AG / NIA NIH HHS / United States
P50 AG008702 / AG / NIA NIH HHS / United States
P50 AG016570 / AG / NIA NIH HHS / United States
P50 AG016573 / AG / NIA NIH HHS / United States
P50 AG016574 / AG / NIA NIH HHS / United States
P50 AG016575 / AG / NIA NIH HHS / United States
P50 AG016576 / AG / NIA NIH HHS / United States
P50 AG016577 / AG / NIA NIH HHS / United States
P50 AG016582 / AG / NIA NIH HHS / United States
P50 AG023501 / AG / NIA NIH HHS / United States
R01 AG017173 / AG / NIA NIH HHS / United States
R01 AG019085 / AG / NIA NIH HHS / United States
R01 AG020688 / AG / NIA NIH HHS / United States
R01 AG025259 / AG / NIA NIH HHS / United States
R01 AG025259 / AG / NIA NIH HHS / United States
R01 AG026916 / AG / NIA NIH HHS / United States
R01 AG027944 / AG / NIA NIH HHS / United States
R01 AG031581 / AG / NIA NIH HHS / United States
R01 AG034504 / AG / NIA NIH HHS / United States
R01 AG05128 / AG / NIA NIH HHS / United States
R01 AG15819 / AG / NIA NIH HHS / United States
R01 AG17917 / AG / NIA NIH HHS / United States
R01 AG30146 / AG / NIA NIH HHS / United States
R01 AG33193 / AG / NIA NIH HHS / United States
R01 CA129769 / CA / NCI NIH HHS / United States
R01 MH080295 / MH / NIMH NIH HHS / United States
R01 MH60451 / MH / NIMH NIH HHS / United States
R01 NS059873 / NS / NINDS NIH HHS / United States
R01 NS39764 / NS / NINDS NIH HHS / United States
R37 AG015473 / AG / NIA NIH HHS / United States
RC2 AG036528 / AG / NIA NIH HHS / United States
RC2 AG036535 / AG / NIA NIH HHS / United States
U01 AG016976 / AG / NIA NIH HHS / United States
U01 AG016976 / AG / NIA NIH HHS / United States
U01 AG024904 / AG / NIA NIH HHS / United States
U01 AG032984 / AG / NIA NIH HHS / United States
U01 AG032984 / AG / NIA NIH HHS / United States
U01 AG06781 / AG / NIA NIH HHS / United States
U01 AG10483 / AG / NIA NIH HHS / United States
U01 HG004610 / HG / NHGRI NIH HHS / United States
U24 AG021886 / AG / NIA NIH HHS / United States
U24 AG026390 / AG / NIA NIH HHS / United States
U24 AG026395 / AG / NIA NIH HHS / United States
U24 AG21886 / AG / NIA NIH HHS / United States
UL1 RR02777 / RR / NCRR NIH HHS / United States
UL1 RR029893 / RR / NCRR NIH HHS / United States
UL1 RR029893 / RR / NCRR NIH HHS / United States
/ / Canadian Institutes of Health Research / Canada
/ / Howard Hughes Medical Institute / United States
/ / Medical Research Council / United Kingdom
/ / Wellcome Trust / United Kingdom