ArticleFrontiers in genetics2019
Pleiotropic Meta-Analysis of Age-Related Phenotypes Addressing Evolutionary Uncertainty in Their Molecular Mechanisms.
Article in Frontiers in genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Pleiotropic Associations with Alzheimer's Disease and Physical Activity: Sex Differences and the Effects of Environment.International journal of molecular sciences · 2024Article
- Article
- Curcumin supplementation increases longevity and antioxidant capacity inFrontiers in pharmacology · 2023Article
- Prevailing Antagonistic Risks in Pleiotropic Associations with Alzheimer's Disease and Diabetes.Journal of Alzheimer's disease : JAD · 2023Article
- Mediation of the APOE associations with Alzheimer's and coronary heart diseases through body mass index and lipids.GeroScience · 2022Article
- Pleiotropic predisposition to Alzheimer's disease and educational attainment: insights from the summary statistics analysis.GeroScience · 2022Article
- Genetic Association Studies of Age-Related Traits: New Perspectives.Advances in geriatric medicine and research · 2021Article
- The Variant rs1784042 of theGenes · 2020Article
- Quantitative and Qualitative Role of Antagonistic Heterogeneity in Genetics of Blood Lipids.The journals of gerontology. Series A, Biological sciences and medical sciences · 2020Article
- Polygenic risk score for disability and insights into disability-related molecular mechanisms.GeroScience · 2019Article
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Authors and funding
8 authors.
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Abstract
Age-related phenotypes are characterized by genetic heterogeneity attributed to an uncertain role of evolution in establishing their molecular mechanisms. Here, we performed univariate and pleiotropic meta-analyses of 24 age-related phenotypes dealing with such evolutionary uncertainty and leveraging longitudinal information. Our analysis identified 237 novel single nucleotide polymorphisms (SNPs) in 199 loci with phenotype-specific (61 SNPs) and pleiotropic (176 SNPs) associations and replicated associations for 160 SNPs in 68 loci in a modest sample of 26,371 individuals from five longitudinal studies. Most pleiotropic associations (65.3%, 115 of 176 SNPs) were impacted by heterogeneity, with the natural-selection-free genetic heterogeneity as its inevitable component. This pleiotropic heterogeneity was dominated (93%, 107 of 115 SNPs) by antagonistic genetic heterogeneity, a phenomenon that is characterized by antagonistic directions of genetic effects for directly correlated phenotypes. Genetic association studies of age-related phenotypes addressing the evolutionary uncertainty in establishing their molecular mechanisms have power to substantially improve the efficiency of the analyses. A dominant form of heterogeneous pleiotropy, antagonistic genetic heterogeneity, provides unprecedented insight into the genetic origin of age-related phenotypes and side effects in medical care that is counter-intuitive in medical genetics but naturally expected when molecular mechanisms of age-related phenotypes are not due to direct evolutionary selection.
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