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- Shyamalika Gopalan
- Department of Ecology and Evolution , Stony Brook University, New York 11790
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- Oana Carja
- Department of Biology , University of Pennsylvania, Philadelphia, Pennsylvania 19104
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- Maud Fagny
- Department of Biostatistics , Harvard T. H. Chan School of Public Health, Boston, Massachusetts 02215
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- Etienne Patin
- Human Evolutionary Genetics , Department of Genomes and Genetics, Institut Pasteur, 75015 Paris, France
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- Justin W Myrick
- Department of Anthropology , University of California, Los Angeles, California 90095
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- Lisa M McEwen
- BC Children’s Hospital Research Institute , Vancouver, V5Z 4H4, Canada
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- Sarah M Mah
- BC Children’s Hospital Research Institute , Vancouver, V5Z 4H4, Canada
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- Michael S Kobor
- BC Children’s Hospital Research Institute , Vancouver, V5Z 4H4, Canada
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- Alain Froment
- Institut de Recherche pour le Développement , 75006 Paris, France
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- Marcus W Feldman
- Department of Biology , Stanford University, California 94305
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- Lluis Quintana-Murci
- Human Evolutionary Genetics , Department of Genomes and Genetics, Institut Pasteur, 75015 Paris, France
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- Brenna M Henn
- Department of Ecology and Evolution , Stony Brook University, New York 11790
説明
<jats:title>Abstract</jats:title> <jats:p>Aging is associated with widespread changes in genome-wide patterns of DNA methylation. Thousands of CpG sites whose tissue-specific methylation levels are strongly correlated with chronological age have been previously identified. However, the majority of these studies have focused primarily on cosmopolitan populations living in the developed world; it is not known if age-related patterns of DNA methylation at these loci are similar across a broad range of human genetic and ecological diversity. We investigated genome-wide methylation patterns using saliva- and whole blood-derived DNA from two traditionally hunting and gathering African populations: the Baka of the western Central African rain forest and the ≠Khomani San of the South African Kalahari Desert. We identified hundreds of CpG sites whose methylation levels are significantly associated with age, thousands that are significant in a meta-analysis, and replicate trends previously reported in populations of non-African descent. We confirmed that an age-associated site in the promoter of the gene ELOVL2 shows a remarkably congruent relationship with aging in humans, despite extensive genetic and environmental variation across populations. We also demonstrate that genotype state at methylation quantitative trait loci (meQTLs) can affect methylation trends at some age-associated CpG sites. Our study explores the relationship between CpG methylation and chronological age in populations of African hunter-gatherers, who rely on different diets across diverse ecologies. While many age-related CpG sites replicate across populations, we show that considering common genetic variation at meQTLs further improves our ability to detect previously identified age associations.</jats:p>
収録刊行物
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- Genetics
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Genetics 206 (3), 1659-1674, 2017-07-01
Oxford University Press (OUP)