ArticleGenetics2019
Inferring the Nature of Missing Heritability in Human Traits Using Data from the GWAS Catalog.
Article in Genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 2 of them syntheses that pooled it.
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Who cites it
22 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Kernel-based gene-environment interaction tests for rare variants with multiple quantitative phenotypes.PloS one · 2022Pooled it
- Lifestyle Risk Score: handling missingness of individual lifestyle components in meta-analysis of gene-by-lifestyle interactions.European journal of human genetics : EJHG · 2021Pooled it
- The hidden geometry of breeding constraints.Nature plants · 2026Review
- Applying traditional and machine learning-based GWAS approaches for marker-trait identification in wheat.Frontiers in plant science · 2025Article
- Polygenic risk score: the potential role in the management of systemic lupus erythematosus.RMD open · 2024Article
- Identifying latent genetic interactions in genome-wide association studies using multiple traits.Genome medicine · 2024Article
- GWAS supported by computer vision identifies large numbers of candidate regulators of in planta regeneration in Populus trichocarpa.G3 (Bethesda, Md.) · 2024Article
- Reviewing the essential roles of remote phenotyping, GWAS and explainable AI in practical marker-assisted selection for drought-tolerant winter wheat breeding.Frontiers in plant science · 2024Review
- Leveraging Single-Cell Populations to Uncover the Genetic Basis of Complex Traits.Annual review of genetics · 2023Review
- Trans-Acting Genotypes Associated with mRNA Expression Affect Metabolic and Thermal Tolerance Traits.Genome biology and evolution · 2023Article
- An eco-evo-devo genetic network model of stress response.Horticulture research · 2022Article
- Multi-Omic Approaches to Identify Genetic Factors in Metabolic Syndrome.Comprehensive Physiology · 2021Article
- Decoding 'Unnecessary Complexity': A Law of Complexity and a Concept of Hidden Variation Behind "Missing Heritability" in Precision Medicine.Journal of molecular evolution · 2021Review
- Meta-analysis: Congruence of genomic and phenotypic differentiation across diverse natural study systems.Evolutionary applications · 2021Article
- Highly pleiotropic variants of human traits are enriched in genomic regions with strong background selection.Human genetics · 2021Article
- Neighbor GWAS: incorporating neighbor genotypic identity into genome-wide association studies of field herbivory.Heredity · 2021Article
- An epigenetic, transgenerational model of increased mental health disorders in children, adolescents and young adults.European journal of human genetics : EJHG · 2021Review
- Genetic risk factors of ME/CFS: a critical review.Human molecular genetics · 2020Review
- Genetic control of non-genetic inheritance in mammals: state-of-the-art and perspectives.Mammalian genome : official journal of the International Mammalian Genome Society · 2020Review
- Accelerated inbreeding depression suggests synergistic epistasis for deleterious mutations in Drosophila melanogaster.Heredity · 2019Article
Corrections and comments
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Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Thousands of genes responsible for many diseases and other common traits in humans have been detected by Genome Wide Association Studies (GWAS) in the last decade. However, candidate causal variants found so far usually explain only a small fraction of the heritability estimated by family data. The most common explanation for this observation is that the missing heritability corresponds to variants, either rare or common, with very small effect, which pass undetected due to a lack of statistical power. We carried out a meta-analysis using data from the NHGRI-EBI GWAS Catalog in order to explore the observed distribution of locus effects for a set of 42 complex traits and to quantify their contribution to narrow-sense heritability. With the data at hand, we were able to predict the expected distribution of locus effects for 16 traits and diseases, their expected contribution to heritability, and the missing number of loci yet to be discovered to fully explain the familial heritability estimates. Our results indicate that, for 6 out of the 16 traits, the additive contribution of a great number of loci is unable to explain the familial (broad-sense) heritability, suggesting that the gap between GWAS and familial estimates of heritability may not ever be closed for these traits. In contrast, for the other 10 traits, the additive contribution of hundreds or thousands of loci yet to be found could potentially explain the familial heritability estimates, if this were the case. Computer simulations are used to illustrate the possible contribution from nonadditive genetic effects to the gap between GWAS and familial estimates of heritability.
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