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Editorial | ONLINE FIRST

TOMM40 Association With Alzheimer Disease Tales of APOE and Linkage Disequilibrium

Rita J. Guerreiro, PhD; John Hardy, PhD
Arch Neurol. 2012;69(10):1243-1244. doi:10.1001/archneurol.2012.1935.
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Twenty years have passed since the first time APOE genotypes were associated with Alzheimer disease (AD): the frequency of the APOE-E4 allele was found to differ significantly (P = .01) between 30 patients with AD selected from 30 families and 91 age-matched unrelated controls.1 This is one of the most replicated observations in biology and, especially since the advent of genome-wide association studies, this particular genetic association has been shown to be true in many cohorts from different populations. Furthermore, since the first genome-wide association studies in AD it was clear that no other locus in the genome would present such a strong association with the disease as that on chromosome 19 around the APOE locus.2 In fact, not only did genetic variants within APOE show association with AD but single-nucleotide polymorphisms (SNPs) around the locus also presented strong associations with the disease. Thus, the whole chromosome region showed association with disease.

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