ArticleScientific reports2015
Complex trait architecture: the pleiotropic model revisited.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.
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Who cites it
7 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection.Nature genetics · 2018Pooled it
- Understanding the Emergence of Schizophrenia in the Light of Human Evolution: New Perspectives in Genetics.Genes, brain, and behavior · 2025Review
- Characterizing the effect of background selection on the polygenicity of brain-related traits.Genomics · 2021Article
- Evaluating the Potential of Younger Cases and Older Controls Cohorts to Improve Discovery Power in Genome-Wide Association Studies of Late-Onset Diseases.Journal of personalized medicine · 2019Article
- Age-related late-onset disease heritability patterns and implications for genome-wide association studies.PeerJ · 2019Article
- Evidence of directional and stabilizing selection in contemporary humans.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- The Nature of Genetic Variation for Complex Traits Revealed by GWAS and Regional Heritability Mapping Analyses.Genetics · 2015Article
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Authors and funding
2 authors.
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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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