SNPs located at CpG sites modulate genome-epigenome interaction

Zhi, Degui; Aslibekyan, Stella; Irvin, Marguerite R.; Claas, Steven A.; Borecki, Ingrid B.; Ordovas, José M.; Absher, Devin; Arnett, Donna K.

doi:10.4161/epi.25501

Cited by 137 publications

(115 citation statements)

References 13 publications

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“…There was also the interesting finding that ApoE methylation patterns tracked with the 3 ApoE functional allelic genetic variants in the order of level of methylation of E4 [ E3/E3 [ E2 for ApoE carriers. Somewhat similar findings had been noted by Wang et al (2008) showing that differences in ApoE methylation between individuals, with and without Alzheimers disease, increased with age, and Zhi et al (2013), also noted that sequence variants at CPG sites may alter methylation status.…”

Section: Apoe Epigenetics and Longevitysupporting

confidence: 64%

Living long and ageing well: is epigenomics the missing link between nature and nurture?

2015

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Human longevity is a complex trait and increasingly we understand that both genes and lifestyle interact in the longevity phenotype. Non-genetic factors, including diet, physical activity, health habits, and psychosocial factors contribute approximately 50% of the variability in human lifespan with another 25% explained by genetic differences. Family clusters of nonagenarian and centenarian siblings, who show both exceptional age-span and health-span, are likely to have inherited facilitatory gene groups, but also have nine decades of life experiences and behaviours which have interacted with their genetic profiles. Identification of their shared genes is just one small step in the link from genes to their physical and psychological profiles. Behavioural genomics is beginning to demonstrate links to biological mechanisms through regulation of gene expression, which directs the proteome and influences the personal phenotype. Epigenetics has been considered the missing link between nature and nurture. Although there is much that remains to be discovered, this article will discuss some of genetic and environmental factors which appear important in good quality longevity and link known epigenetic mechanisms to themes identified by nonagenarians themselves related to their longevity. Here we suggest that exceptional 90-year old siblings have adopted a range of behaviours and life-styles which have contributed to their ageing-well-phenotype and which link with important public health messages.

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Section: Apoe Epigenetics and Longevitysupporting

confidence: 64%

Living long and ageing well: is epigenomics the missing link between nature and nurture?

2015

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“…Zhang et al, 2010; X. Zhang et al, 2014; Zhi et al, 2013). Many meQTL studies prioritized on the local genetic associations with DNA methylation sites (i.e.…”

Section: Genetic and Environmental Determinants Of Epigenomic Tramentioning

confidence: 99%

Integrative Analysis of Multi-omics Data for Discovery and Functional Studies of Complex Human Diseases

Sun

2016

Advances in Genetics

338

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Complex and dynamic networks of molecules are involved in human diseases. High-throughput technologies enable omics studies interrogating thousands to millions of makers with similar biochemical properties (e.g. transcriptomics for RNA transcripts). However, a single layer of ‘omics’ can only provide limited insights into the biological mechanisms of a disease. In the case of GWAS, although thousands of SNPs have been identified for complex diseases and traits, the functional implications and mechanisms of the associated loci are largely unknown. Additionally, the genomic variants alone are not able to explain the changing disease risk across the life span. DNA, RNA, protein, and metabolite often have complementary roles to jointly perform a certain biological function. Such complementary effects and synergistic interactions between omic layers in the life-course can only be captured by integrative study of multiple molecular layers. Building upon the success in single-omics discovery research, population studies started adopting the multi-omics approach to better understanding the molecular function and disease etiology. Multi-omics approaches integrate data obtained from different omic levels to understand their interrelation and combined influence on the disease processes. Here, we summarize major omics approaches available in population research, and review integrative approaches and methodologies interrogating multiple omic layers, which enhance the gene discovery and functional analysis of human diseases. We seek to provide analytical recommendations for different types of multi-omics data and study designs to guide the emerging multi-omic research, and to suggest improvement of the existing analytical methods.

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“…In the case of methylation, one of the simplest examples involves polymorphic CpG sites [37]. If a nucleotide substitution ablates a CpG in some individuals, those individuals cannot be methylated at that locus.…”

Section: Epigenetics Overviewmentioning

confidence: 99%

The role of epigenomics in personalized medicine

Kronfol

Dozmorov

Huang

et al. 2017

Expert Review of Precision Medicine and Drug Development

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Introduction Epigenetics is the study of reversible modifications to chromatin and their extensive and profound effects on gene regulation. To date, the role of epigenetics in personalized medicine has been under-explored. Therefore, this review aims to highlight the vast potential that epigenetics holds. Areas covered We first review the cell-specific nature of epigenetic states and how these can vary with developmental stage and in response to environmental factors. We then summarize epigenetic biomarkers of disease, with a focus on diagnostic tests, followed by a detailed description of current and pipeline drugs with epigenetic modes of action. Finally, we discuss epigenetic biomarkers of drug response. Expert commentary Epigenetic variation can yield information on cellular states and developmental histories in ways that genotype information cannot. Furthermore, in contrast to fixed genome sequence, epigenetic patterns are plastic, so correcting aberrant, disease-causing epigenetic marks holds considerable therapeutic promise. While just six epigenetic drugs are currently approved for use in the United States, a larger number is being developed. However, a drawback to current therapeutics is their non-specific effects. Development of locus-specific epigenetic modifiers, used in conjunction with epigenetic biomarkers of response, will enable truly precision interventions.

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SNPs located at CpG sites modulate genome-epigenome interaction

Cited by 137 publications

References 13 publications

Living long and ageing well: is epigenomics the missing link between nature and nurture?

Living long and ageing well: is epigenomics the missing link between nature and nurture?

Integrative Analysis of Multi-omics Data for Discovery and Functional Studies of Complex Human Diseases

The role of epigenomics in personalized medicine

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