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Coordinated Action of Biological Processes during Embryogenesis Can Cause Genome-Wide Linkage Disequilibrium in the Human Genome and Influence Age-Related Phenotypes.

dc.contributor.author Culminskaya, Irina
dc.contributor.author Kulminski, Alexander M
dc.contributor.author Yashin, Anatoli I
dc.coverage.spatial United States
dc.date.accessioned 2017-06-05T15:14:12Z
dc.date.available 2017-06-05T15:14:12Z
dc.date.issued 2016
dc.identifier https://www.ncbi.nlm.nih.gov/pubmed/28357417
dc.identifier.uri https://hdl.handle.net/10161/14797
dc.description.abstract A role of non-Mendelian inheritance in genetics of complex, age-related traits is becoming increasingly recognized. Recently, we reported on two inheritable clusters of SNPs in extensive genome-wide linkage disequilibrium (LD) in the Framingham Heart Study (FHS), which were associated with the phenotype of premature death. Here we address biologically-related properties of these two clusters. These clusters have been unlikely selected randomly because they are functionally and structurally different from matched sets of randomly selected SNPs. For example, SNPs in LD from each cluster are highly significantly enriched in genes (p=7.1×10(-22) and p=5.8×10(-18)), in general, and in short genes (p=1.4×10(-47) and p=4.6×10(-7)), in particular. Mapping of SNPs in LD to genes resulted in two, partly overlapping, networks of 1764 and 4806 genes. Both these networks were gene enriched in developmental processes and in biological processes tightly linked with development including biological adhesion, cellular component organization, locomotion, localization, signaling, (p<10(-4), q<10(-4) for each category). Thorough analysis suggests connections of these genetic networks with different stages of embryogenesis and highlights biological interlink of specific processes enriched for genes from these networks. The results suggest that coordinated action of biological processes during embryogenesis may generate genome-wide networks of genetic variants, which may influence complex age-related phenotypes characterizing health span and lifespan.
dc.language eng
dc.relation.ispartof Ann Gerontol Geriatr Res
dc.subject Age-related traits
dc.subject Embryogenesis
dc.subject Functional linkage
dc.subject Healthspan
dc.subject Linkage disequilibrium
dc.title Coordinated Action of Biological Processes during Embryogenesis Can Cause Genome-Wide Linkage Disequilibrium in the Human Genome and Influence Age-Related Phenotypes.
dc.type Journal article
duke.contributor.id Yashin, Anatoli I|0115822
pubs.author-url https://www.ncbi.nlm.nih.gov/pubmed/28357417
pubs.issue 1
pubs.organisational-group Center for Population Health & Aging
pubs.organisational-group Duke
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Duke Population Research Center
pubs.organisational-group Duke Population Research Institute
pubs.organisational-group Institutes and Centers
pubs.organisational-group Institutes and Provost's Academic Units
pubs.organisational-group Sanford School of Public Policy
pubs.organisational-group School of Medicine
pubs.organisational-group Social Science Research Institute
pubs.organisational-group University Institutes and Centers
pubs.publication-status Published
pubs.volume 3


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