Thursday, June 20, 2013

Missing heritability (in progress)

What is the definition? Does it only apply to additive variance? It should, because of the linear model used.

Wikipedia gives a good explanation for broad and narrow sense heritability. The narrow sense heritability is
   h^2 = Var(A) / Var(P)
where Var(A) refers to the additive genetic variance (?).

In human, common SNPs are defined as >5% for major allele frequency (MAF)?

Eric Lander explain phantom heritability at 1hour timepoint in this video (May 20, 2011). Lander basically thinks linear additive model is inadequate to describe the biological mechanism. Lander and Francis Colin had an interesting exchange on independent loci, additive effect. (About 1:12 in this video).
http://videocast.nih.gov/Summary.asp?File=16668

Nature reviews genetics have some interesting 'Viewpoints' on the missing heritability problem. Gibson seems to think it due to mistreatment of environmental factors.

A blog "Genetic Inference" defended the additivity model, and cited some evolutionary arguments on additivity.

A Discovery blog explains, "the missing heritability can be solved by reconceptualizing the “genetic architecture” of the trait. This means that currently a major assumption of many models for putatively polygenic traits is that the variation is due to many genes of small effect which modify the trait value in an additive and independent manner. In other words, the genetic architecture in this sense is a linear system. A clear alternative, or complementary, possibility is that there are genetic interactions which are generating deviations from linearity. This would be epistasis, which has different implications depending on the sort of biology you’re talking about (e.g., molecular vs. evolutionary)." Some comments on this blog are worth reading.

Hemani et al 2012, argued that non-additive genetic variance contributed to the missing heritability problem.




References:
Zuk et al 2012, PNAS
http://en.wikipedia.org/wiki/Heritability#Definition
http://en.wikipedia.org/wiki/Missing_heritability_problem

Related artilce on mathematic modeling of epistatiss
Gjuvsland 2007 Genetics, statistical epistatsis is a generic feature of gene regulatory networks.

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