Complex trait architecture: the pleiotropic model revisited

Scientific Reports
T-L North, M A Beaumont

Abstract

There is currently much debate about how much the genetic heritability of complex traits is due to very rare alleles. This issue is important because it determines sampling strategies for genetic association studies. Several recent theoretical papers based on a pleiotropic model for trait evolution suggest that it is possible that a large proportion of the genetic variance could be explained by rare alleles. This model assumes that mutations with a large effect on fitness also tend to have large positive or negative effects on phenotypic traits. We show that conclusions based on standard diffusion results are generally applicable to simulations of whole genomes with overlapping generations in a finite population, although the variance contribution of rare alleles is somewhat smaller than theoretical predictions. We show that under many scenarios the pleiotropic model predicts trait distributions that are unrealistically leptokurtic. We argue that this imposes a limit on the relationship between fitness and trait effects.

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Citations

Dec 20, 2017·Proceedings of the National Academy of Sciences of the United States of America·Jaleal S SanjakPeter M Visscher

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Methods Mentioned

BETA
genotyping

Software Mentioned

glkerns
R lokern
GNU GSL library
R Core
R
Mathematica

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