Abstract
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.
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Acknowledgements
This chapter was partly supported by the National Institute on Aging of the National Institutes of Health under Award Numbers R01AG030198, R01AG032319, R01AG030612, R01AG046860, and P01AG043352. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The Framingham Heart Study (FHS) is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with Boston University (Contract No. N01-HC-25195). This chapter was not prepared in collaboration with investigators of the FHS and does not necessarily reflect the opinions or views of the FHS, Boston University, or NHLBI. Funding for SHARe Affymetrix genotyping was provided by NHLBI Contract N02-HL-64278. SHARe Illumina genotyping was provided under an agreement between Illumina and Boston University. This work was prepared using a limited access dataset obtained from the NHLBI and the Framingham SHARe data obtained through dbGaP.
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Kulminski, A.M., Yashin, A.I., Culminskaya, I., Land, K.C., Ukraintseva, S.V. (2016). The Complex Role of Genes in Diseases and Traits in Late Life: An Example of the Apolipoprotein E Polymorphism. In: Biodemography of Aging. The Springer Series on Demographic Methods and Population Analysis, vol 40. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-7587-8_9
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