ArticlePLoS computational biology2012
Parameters in dynamic models of complex traits are containers of missing heritability.
Article in PLoS computational biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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
15 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Association between the HTR1A rs6295 gene polymorphism and suicidal behavior: an updated meta-analysis.European archives of psychiatry and clinical neuroscience · 2023Pooled it
- The limitations of phenotype prediction in metabolism.PLoS computational biology · 2023Article
- Using a system of differential equations that models cattle growth to uncover the genetic basis of complex traits.Journal of applied genetics · 2017Article
- Comparing GWAS Results of Complex Traits Using Full Genetic Model and Additive Models for Revealing Genetic Architecture.Scientific reports · 2017Article
- Network biology concepts in complex disease comorbidities.Nature reviews. Genetics · 2016Review
- Towards causally cohesive genotype-phenotype modelling for characterization of the soft-tissue mechanics of the heart in normal and pathological geometries.Journal of the Royal Society, Interface · 2015Article
- Causal drift, robust signaling, and complex disease.PloS one · 2015Article
- Article
- Missing heritability of common diseases and treatments outside the protein-coding exome.Human genetics · 2014Review
- Genetic regulatory network motifs constrain adaptation through curvature in the landscape of mutational (co)variance.Evolution; international journal of organic evolution · 2014Article
- Review
- PGMRA: a web server for (phenotype x genotype) many-to-many relation analysis in GWAS.Nucleic acids research · 2013Article
- Bridging the genotype-phenotype gap: what does it take?The Journal of physiology · 2013Review
- Effect of regulatory architecture on broad versus narrow sense heritability.PLoS computational biology · 2013Article
- Interpreting genetic effects through models of cardiac electromechanics.American journal of physiology. Heart and circulatory physiology · 2012Review
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Polymorphisms identified in genome-wide association studies of human traits rarely explain more than a small proportion of the heritable variation, and improving this situation within the current paradigm appears daunting. Given a well-validated dynamic model of a complex physiological trait, a substantial part of the underlying genetic variation must manifest as variation in model parameters. These parameters are themselves phenotypic traits. By linking whole-cell phenotypic variation to genetic variation in a computational model of a single heart cell, incorporating genotype-to-parameter maps, we show that genome-wide association studies on parameters reveal much more genetic variation than when using higher-level cellular phenotypes. The results suggest that letting such studies be guided by computational physiology may facilitate a causal understanding of the genotype-to-phenotype map of complex traits, with strong implications for the development of phenomics technology.
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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.