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.
Guerreiro RJ, Hardy J. TOMM40 Association With Alzheimer DiseaseTales of APOE and Linkage Disequilibrium. Arch Neurol. 2012;69(10):1243–1244. doi:10.1001/archneurol.2012.1935
Customize your JAMA Network experience by selecting one or more topics from the list below.