Data and Theory Point to Mainly Additive Genetic Variance for Complex Traits

By W. G. Hill, Michael E. Goddard, Peter M. Visscher. PLoS Genetics, 2008

1,053 citations recorded by the source corpus.

The relative proportion of additive and non-additive variation for complex traits is important in evolutionary biology, medicine, and agriculture. We address a long-standing controversy and paradox about the contribution of non-additive genetic variation, namely that knowledge about biological pathways and gene networks imply that epistasis is important. Yet empirical data across a range of traits and species imply that most genetic variance is additive. We evaluate the evidence from empirical studies of genetic variance components and find that additive variance typically accounts for over half, and often close to 100%, of the total genetic variance. We present new theoretical results, based upon the distribution of allele frequencies under neutral and other population genetic models, that show why this is the case even if there are non-additive effects at the level of gene action. We conclude that interactions at the level of genes are not likely to generate much interaction at the level of variance.

Subfields: Genetics

View Paper: https://www.semanticscholar.org/paper/19b13aa2e33a5c1b3ed159fe950da3e474a2246e

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Genetics

Citations in the corpus

Missing heritability and strategies for finding the underlying causes of complex disease (2010, background): “, and theoretical models and data have already been used to argue that additive genetic effects are likely to be common in complex phenotype”
Potential for evolutionary responses to climate change – evidence from tree populations (2013, result): “These findings are consistent with the small effect sizes of flowering time and leaf trait variation loci in maize (Buckler et al., 2009; Tian et al., 2011), and human height (Hill et al., 2008).”
Genetic confounding of the relationship between father absence and age at menarche (2017, background): “With that in mind, Hill, Goddard, and Visscher (2008) provided evidence suggesting that additive variance accounts for the majority of genetic variance in many traits.”
The mystery of missing heritability: Genetic interactions create phantom heritability (2012, neutral): “(23) for 86 traits (SI Appendix, section 5.”
Genomic selection in forest tree breeding: the concept and an outlook to the future (2014, background): “that most of the traits of interest to improve such as growth and yield have complex inheritance patterns (Hill et al. 2008).”
Epistasis—the essential role of gene interactions in the structure and evolution of genetic systems (2008, background): “There seems to be little evidence that epistatic variance has an important role in most population”
Correlation and Causation in the Study of Personality (2012, background): “The causal and statistical definitions of the average effect can coincide if gene action is purely additive, and both population-genetic theory and the available data suggest that for many traits pure additivity should be an acceptable approximation (Crow, 2010; Hill et al., 2008).”
Estimating Effects and Making Predictions from Genome-Wide Marker Data (2010, background): “Hill et al. (2008) [26] argue that the nonadditive variance is typically smaller than the additive genetic variance and, if so, this would suggest that additive models would be at least the first step in predicting phenotype.”
Genomic Selection for Crop Improvement (2017, positive): “There is current debate, at both theoretical and empirical levels, of the likely importance of epistasis in the architecture of quantitative traits (Carlborg and Haley, 2004; Hill et al., 2008; Holland, 2007; Mackay, 2008).”
Inaugural Article: Epistasis dominates the genetic architecture of Drosophila quantitative traits (2012, positive): “Controversy about the relative importance of epistasis in the genetic architecture of complex traits began with early formulations of quantitative genetic theory (7, 8) and continues today (9, 10).”