ArticleProceedings of the National Academy of Sciences of the United States of America2008
Genetic architecture of complex traits: large phenotypic effects and pervasive epistasis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 156 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
156 citing papers in PubMed, 1 synthesis or guideline pooled it, 266 citations in OpenAlex.
- Genetic architecture of growth traits revealed by global epistatic interactions.Genome biology and evolution · 2011Pooled it
- Quantitative trait loci, G×E and G×G for glycemic traits: response to metformin and placebo in the Diabetes Prevention Program (DPP).Journal of human genetics · 2022Trial
- Deconstruction ofbioRxiv : the preprint server for biology · 2026Article
- A programmable platform enabling targeted chromosome substitution and cross-species stability profiling.Protein & cell · 2026Article
- Epistasis and cryptic QTL identified using modified bulk segregant analysis of copper resistance in budding yeast.Genetics · 2025Article
- Epistasis and cryptic QTL identified using modified bulk segregant analysis of copper resistance in budding yeast.bioRxiv : the preprint server for biology · 2024Article
- Pleiotropy, epistasis and the genetic architecture of quantitative traits.Nature reviews. Genetics · 2024Review
- Genetic analysis of cassava brown streak disease root necrosis using image analysis and genome-wide association studies.Frontiers in plant science · 2024Article
- Factorizing polygenic epistasis improves prediction and uncovers biological pathways in complex traits.American journal of human genetics · 2023Article
- Leveraging the genetic correlation between traits improves the detection of epistasis in genome-wide association studies.G3 (Bethesda, Md.) · 2023Article
- Unveiling the Mysteries of Non-Mendelian Heredity in Plant Breeding.Plants (Basel, Switzerland) · 2023Review
- Allograft inflammatory factor-1-like is a situational regulator of leptin levels, hyperphagia, and obesity.iScience · 2022Article
- Biomarker interaction selection and disease detection based on multivariate gain ratio.BMC bioinformatics · 2022Article
- The interplay of additivity, dominance, and epistasis on fitness in a diploid yeast cross.Nature communications · 2022Article
- Genetic basis of a spontaneous mutation's expressivity.Genetics · 2022Article
- Review
- Genetic prediction of complex traits with polygenic scores: a statistical review.Trends in genetics : TIG · 2021Review
- A model and test for coordinated polygenic epistasis in complex traits.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- The complex role of genetic background in shaping the effects of spontaneous and induced mutations.Yeast (Chichester, England) · 2021Review
- Competitive history shapes rapid evolution in a seasonal climate.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
96 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 7 institutions in 1 country.
Funding
Abstract
The genetic architecture of complex traits underlying physiology and disease in most organisms remains elusive. We still know little about the number of genes that underlie these traits, the magnitude of their effects, or the extent to which they interact. Chromosome substitution strains (CSSs) enable statistically powerful studies based on testing engineered inbred strains that have single, unique, and nonoverlapping genetic differences, thereby providing measures of phenotypic effects that are attributable to individual chromosomes. Here, we report a study of phenotypic effects and gene interactions for 90 blood, bone, and metabolic traits in a mouse CSS panel and 54 traits in a rat CSS panel. Two key observations emerge about the genetic architecture of these traits. First, the traits tend to be highly polygenic: across the genome, many individual chromosome substitutions each had significant phenotypic effects and, within each of the chromosomes studied, multiple distinct loci were found. Second, strong epistasis was found among the individual chromosomes. Specifically, individual chromosome substitutions often conferred surprisingly large effects (often a substantial fraction of the entire phenotypic difference between the parental strains), with the result that the sum of these individual effects often dramatically exceeded the difference between the parental strains. We suggest that strong, pervasive epistasis may reflect the presence of several phenotypically-buffered physiological states. These results have implications for identification of complex trait genes, developmental and physiological studies of phenotypic variation, and opportunities to engineer phenotypic outcomes in complex biological systems.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.