ArticleNature genetics2013
Evaluating empirical bounds on complex disease genetic architecture.
Article in Nature genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.
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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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Who cites it
86 citing papers in PubMed.
- Genetic architectures of brain-related traits are shaped by strong selective constraints.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Genetic architectures of brain-related traits are shaped by strong selective constraints.bioRxiv : the preprint server for biology · 2026Article
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- Association between asthma and type 2 diabetes in a Swedish adult population: a register-based cross-sectional study.Thorax · 2025Article
- How (Ultra-)Rare Gene Variants Improve Our Understanding of More Common Autoimmune and Inflammatory Diseases.ACR open rheumatology · 2025Review
- Evolutionary Action-Machine Learning Model Identifies Candidate Genes Associated With Early-Onset Coronary Artery Disease.Journal of the American Heart Association · 2023Article
- The genetics of non-monogenic IBD.Human genetics · 2023Review
- Mapping genomic regulation of kidney disease and traits through high-resolution and interpretable eQTLs.Nature communications · 2023Article
- Identification of prolactin receptor variants with diverse effects on receptor signalling.Journal of molecular endocrinology · 2023Article
- Missense Variants of von Willebrand Factor in the Background of COVID-19 Associated Coagulopathy.Genes · 2023Article
- The genetics of autoimmune Addison disease: past, present and future.Nature reviews. Endocrinology · 2022Review
- Canalization of the Polygenic Risk for Common Diseases and Traits in the UK Biobank Cohort.Molecular biology and evolution · 2022Article
- Identification of heritable rare variants associated with early-stage lung adenocarcinoma risk.Translational lung cancer research · 2022Article
- Ultrafast homomorphic encryption models enable secure outsourcing of genotype imputation.Cell systems · 2021Article
- Clinical relevance of targeted exome sequencing in patients with rare syndromic short stature.Orphanet journal of rare diseases · 2021Article
- Maintenance of Complex Trait Variation: Classic Theory and Modern Data.Frontiers in genetics · 2021Review
- Article
- Evolutionary perspectives on polygenic selection, missing heritability, and GWAS.Human genetics · 2020Review
- Extreme Polygenicity of Complex Traits Is Explained by Negative Selection.American journal of human genetics · 2019Article
- Article
26 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
The genetic architecture of human diseases governs the success of genetic mapping and the future of personalized medicine. Although numerous studies have queried the genetic basis of common disease, contradictory hypotheses have been advocated about features of genetic architecture (for example, the contribution of rare versus common variants). We developed an integrated simulation framework, calibrated to empirical data, to enable the systematic evaluation of such hypotheses. For type 2 diabetes (T2D), two simple parameters--(i) the target size for causal mutation and (ii) the coupling between selection and phenotypic effect--define a broad space of architectures. Whereas extreme models are excluded by the combination of epidemiology, linkage and genome-wide association studies, many models remain consistent, including those where rare variants explain either little (<25%) or most (>80%) of T2D heritability. Ongoing sequencing and genotyping studies will further constrain the space of possible architectures, but very large samples (for example, >250,000 unselected individuals) will be required to localize most of the heritability underlying T2D and other traits characterized by these models.
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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.