Topic
Pleiotropy
About: Pleiotropy is a research topic. Over the lifetime, 1141 publications have been published within this topic receiving 58155 citations. The topic is also known as: Pleiotropism & Genetic Pleiotropy.
Papers published on a yearly basis
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Papers
TL;DR: The MR-PRESSO test detects and corrects horizontal pleiotropy in multi-instrument Mendelian randomization (MR) analyses and introduces distortions in the causal estimates in MR that ranged on average from –131% to 201%; it is shown using simulations that the MR-pressO test is best suited when horizontal Pleiotropy occurs in <50% of instruments.
Abstract: Horizontal pleiotropy occurs when the variant has an effect on disease outside of its effect on the exposure in Mendelian randomization (MR). Violation of the ‘no horizontal pleiotropy’ assumption can cause severe bias in MR. We developed the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) test to identify horizontal pleiotropic outliers in multi-instrument summary-level MR testing. We showed using simulations that the MR-PRESSO test is best suited when horizontal pleiotropy occurs in 48% of causal relationships.
6,742 citations
TL;DR: August Weismann's theory is subject to a number of criticisms, the most forceful of which are: 1) The fallacy of identifying senescence with mechanical wear, 2) the extreme rarity, in natural populations, of individuals that would be old enough to die of the postulated death-mechanism, 3) the failure of several decades of gerontological research to uncover any deathmechanisms, and 4) the difficulties involved in visualizing how such a feature could be produced
Abstract: A new individual entering a population may be said to have a reproductive probability distribution. The reproductive probability is zero from zygote to reproductive maturity. Later, perhaps shortly...
4,543 citations
Journal Article•
TL;DR: A new individual entering a population may be said to have a reproductive probability distribution as discussed by the authors, where the reproductive probability is zero from zygote to reproductive maturity, i.e., the individual will have no reproductive capability from birth to maturity.
Abstract: A new individual entering a population may be said to have a reproductive probability distribution. The reproductive probability is zero from zygote to reproductive maturity. Later, perhaps shortly...
4,202 citations
TL;DR: It is demonstrated that 102 mutational trajectories linking β-lactamase alleles are inaccessible to Darwinian selection and that many of the remaining trajectories have negligible probabilities of realization, which implies that the protein tape of life may be largely reproducible and even predictable.
Abstract: Five point mutations in a particular β-lactamase allele jointly increase bacterial resistance to a clinically important antibiotic by a factor of ∼100,000. In principle, evolution to this high-resistance β-lactamase might follow any of the 120 mutational trajectories linking these alleles. However, we demonstrate that 102 trajectories are inaccessible to Darwinian selection and that many of the remaining trajectories have negligible probabilities of realization, because four of these five mutations fail to increase drug resistance in some combinations. Pervasive biophysical pleiotropy within the β-lactamase seems to be responsible, and because such pleiotropy appears to be a general property of missense mutations, we conclude that much protein evolution will be similarly constrained. This implies that the protein tape of life may be largely reproducible and even predictable.
1,396 citations
TL;DR: This review outlines how newly developed methods can be used together to improve the reliability of Mendelian randomization and discusses the burgeoning treasure trove of genetic associations yielded through genome wide association studies.
Abstract: Pleiotropy, the phenomenon of a single genetic variant influencing multiple traits, is likely widespread in the human genome. If pleiotropy arises because the single nucleotide polymorphism (SNP) influences one trait, which in turn influences another ('vertical pleiotropy'), then Mendelian randomization (MR) can be used to estimate the causal influence between the traits. Of prime focus among the many limitations to MR is the unprovable assumption that apparent pleiotropic associations are mediated by the exposure (i.e. reflect vertical pleiotropy), and do not arise due to SNPs influencing the two traits through independent pathways ('horizontal pleiotropy'). The burgeoning treasure trove of genetic associations yielded through genome wide association studies makes for a tantalizing prospect of phenome-wide causal inference. Recent years have seen substantial attention devoted to the problem of horizontal pleiotropy, and in this review we outline how newly developed methods can be used together to improve the reliability of MR.
1,321 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2025 | 118 |
| 2024 | 205 |
| 2023 | 296 |
| 2022 | 343 |
| 2021 | 115 |
| 2020 | 89 |