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. 2012 Oct;69(10):1270-9.
doi: 10.1001/archneurol.2012.2052.

Comprehensive search for Alzheimer disease susceptibility loci in the APOE region

Gyungah Jun  1 , Badri N Vardarajan, Jacqueline Buros, Chang-En Yu, Michele V Hawk, Beth A Dombroski, Paul K Crane, Eric B Larson; Alzheimer's Disease Genetics Consortium; Richard Mayeux, Jonathan L Haines, Kathryn L Lunetta, Margaret A Pericak-Vance, Gerard D Schellenberg, Lindsay A Farrer
Collaborators, Affiliations

Comprehensive search for Alzheimer disease susceptibility loci in the APOE region

Gyungah Jun et al. Arch Neurol. 2012 Oct.

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.

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Figures

Figure 1
Figure 1
Distribution of TOMM40 rs10524523 genotypes (derived from combinations of the short [s], long [l], and very long [v] alleles) according to apolipoprotein E (APOE) genotype in the Adult Changes in Thought Study (A), National Institute on Aging Alzheimer's Disease Centers (B), Alzheimer's Disease Neuroimaging Initiative Study (C), and the combined (D) data sets.
Figure 2
Figure 2
Survival analysis curves for age at onset of Alzheimer disease in the Adult Changes in Thought Study (A and B), National Institute on Aging Alzheimer's Disease Centers (C and D), and Alzheimer's Disease Neuroimaging Initiative Study (E and F) data sets. The effect of the presence or absence of the TOMM40 long (l) allele at rs10524523 and of the apolipoprotein E (APOE) ε4 allele on age at onset is shown in all subjects (A, C, and E) and in the APOE ε3/ε3 subgroup (B, D, and E). s Indicates short allele and v, very long allele.
See this image and copyright information in PMC

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References

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