The Complex Role of Genes in Diseases and Traits in Late Life: An Example of the Apolipoprotein E Polymorphism
Decades of studies of candidate genes show that they are not linked to aging-related traits in a straightforward manner. Recent genome-wide association studies (GWAS) have reached fundamentally the same conclusion by showing that traits in late life are likely controlled by a relatively large number of common genetic variants. Further, GWAS often show that the associations are of tiny effect. The primary reason for complex actions of genes on age-related traits characteristic of modern societies is the elusive role of evolution in these traits. Therefore, the complexity of gene actions on traits in late life appears to be inherent. The complexity of gene actions on traits in late life can well explain why many genetic signals appear to be weak. In this chapter, we consider several examples of complex modes of gene actions, including genetic tradeoffs, antagonistic genetic effects on the same traits at different ages, and variable genetic effects on lifespan. The analyses focus on the APOE common polymorphism.
