Abstract
Recent developments in the collection and analysis of cellular multilayered data in large cohorts with extensive organismal phenotyping promise to reveal links between genetic variation and biological processes. The use of these cellular resources as models for human biology — known as 'cellular phenotyping' — is likely to transform our understanding of the genetic and long-term environmental influences on complex traits. I discuss the advantages and caveats of a deeper analysis of cellular phenotypes in large cohorts and assess the methodological advances, resource needs and prospects of this new approach.
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The author would like to thank the Louis-Jeantet Foundation and the Swiss National Science Foundation for support.
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Glossary
- Additive
-
In the context of a genetic effect, the linear relationship between the replacement of an allele and its effect on the phenotype.
- Expression quantitative trait loci
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(eQTLs). Loci at which genetic allelic variation is associated with variation in gene expression.
- Induced pluripotent stem cells
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(iPSCs). Cells that are derived from somatic cells by 'reprogramming' or de-differentiation that is triggered by the transfection of pluripotency genes, which alters the somatic cells to a state that is similar to that of embryonic stem cells.
- Marginal effects
-
Also known as main effects, these are the effects of a variable assuming no dependency or conditionality of other variables.
- Metabolomics
-
The directed use of quantitative analytical methods for analysing the entire metabolic content of a cell or organism (that is, the metabolome) at a given time.
- Purifying natural selection
-
Natural selection that results in the reduction or elimination of the frequency of alleles with negative fitness effects.
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Dermitzakis, E. Cellular genomics for complex traits. Nat Rev Genet 13, 215–220 (2012). https://doi.org/10.1038/nrg3115
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DOI: https://doi.org/10.1038/nrg3115