ArticlePLoS genetics2017
Genetic loci associated with coronary artery disease harbor evidence of selection and antagonistic pleiotropy.
Article in PLoS genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 2 of them syntheses that pooled it.
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Who cites it
38 citing papers in PubMed, 2 syntheses or guidelines pooled it, 72 citations in OpenAlex.
- Multivariate genomic scan implicates novel loci and haem metabolism in human ageing.Nature communications · 2020Pooled it
- Effects of blood lead on coronary artery disease and its risk factors: a Mendelian Randomization study.Scientific reports · 2019Pooled it
- No genome-wide correlations and little shared genetic architecture between reproductive life-history traits and estrogen receptor-positive breast cancer risk.Molecular biology and evolution · 2026Article
- Evolutionary genetics of ageing.Nature reviews. Genetics · 2026Review
- Genetic trade-offs in fertility and longevity explain the maintenance of disease-associated alleles in humans.Nature ecology & evolution · 2026Article
- Extensive antagonistic variants across the human genome.Nature communications · 2026Article
- Genetic and functional evidence implicates amedRxiv : the preprint server for health sciences · 2025Article
- Integrating the Thrifty Genotype and Evolutionary Mismatch Hypotheses to understand variation in cardiometabolic disease risk.Evolution, medicine, and public health · 2024Review
- Evidence for the role of selection for reproductively advantageous alleles in human aging.Science advances · 2023Article
- A deep catalog of protein-coding variation in 985,830 individuals.bioRxiv : the preprint server for biology · 2023Article
- Leveraging molecular quantitative trait loci to comprehend complex diseases/traits from the omics perspective.Human genetics · 2023Review
- Applying an evolutionary mismatch framework to understand disease susceptibility.PLoS biology · 2023Article
- Mosaic patterns of selection in genomic regions associated with diverse human traits.PLoS genetics · 2022Article
- Dissecting Polygenic Etiology of Ischemic Stroke in the Era of Precision Medicine.Journal of clinical medicine · 2022Review
- Evolutionary medicine.eLife · 2021Article
- The influence of evolutionary history on human health and disease.Nature reviews. Genetics · 2021Review
- Genetic Variants in Transcription Factor Binding Sites in Humans: Triggered by Natural Selection and Triggers of Diseases.International journal of molecular sciences · 2021Review
- Polygenic Risk Scores Augment Stroke Subtyping.Neurology. Genetics · 2021Article
- Predicting evolutionary change at the DNA level in a natural Mimulus population.PLoS genetics · 2021Article
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Corrections and comments
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Authors and funding
8 authors at 4 institutions in 4 countries.
Funding
Abstract
Traditional genome-wide scans for positive selection have mainly uncovered selective sweeps associated with monogenic traits. While selection on quantitative traits is much more common, very few signals have been detected because of their polygenic nature. We searched for positive selection signals underlying coronary artery disease (CAD) in worldwide populations, using novel approaches to quantify relationships between polygenic selection signals and CAD genetic risk. We identified new candidate adaptive loci that appear to have been directly modified by disease pressures given their significant associations with CAD genetic risk. These candidates were all uniquely and consistently associated with many different male and female reproductive traits suggesting selection may have also targeted these because of their direct effects on fitness. We found that CAD loci are significantly enriched for lifetime reproductive success relative to the rest of the human genome, with evidence that the relationship between CAD and lifetime reproductive success is antagonistic. This supports the presence of antagonistic-pleiotropic tradeoffs on CAD loci and provides a novel explanation for the maintenance and high prevalence of CAD in modern humans. Lastly, we found that positive selection more often targeted CAD gene regulatory variants using HapMap3 lymphoblastoid cell lines, which further highlights the unique biological significance of candidate adaptive loci underlying CAD. Our study provides a novel approach for detecting selection on polygenic traits and evidence that modern human genomes have evolved in response to CAD-induced selection pressures and other early-life traits sharing pleiotropic links with CAD.
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Registered trials
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