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Systems genetics of alcoholism.

Sloan CD, Sayarath V, Moore JH - Alcohol Res Health (2008)

Bottom Line: Systems genetics is the study of all genetic variations, their interactions with each other (i.e., epistasis), their interactions with the environment (i.e., plastic reaction norms), their relationship with interindividual variation in traits that are influenced by many genes and contribute to disease susceptibility (i.e., intermediate quantitative traits or endophenotypes) defined at different levels of hierarchical biochemical and physiological systems, and their relationship with health and disease. (An endophenotype is a genetically determined trait [i.e., phenotype] that is not immediately visible but may contribute to the susceptibility to develop a particular behavior or syndrome.See the glossary, p. 84, for descriptions of other technical terms used in this article.) The goal of systems genetics is to provide an understanding of the complex relationship between the genome and disease by investigating intermediate biological processes.After investigating main effects, the first step in a systems genetics approach, as described here, is to search for gene-gene (i.e., epistatic) reactions.

View Article: PubMed Central - PubMed

Affiliation: Section of Epidemiology and Biostatistics, Department of Community and Family Medicine, Dartmouth Medical School, Lebanon, New Hampshire.

ABSTRACT
Alcoholism is a common disease resulting from the complex interaction of genetic, social, and environmental factors. Interest in the high heritability of alcoholism has resulted in many studies of how single genes, as well as an individual's entire genetic content (i.e., genome) and the proteins expressed by the genome, influence alcoholism risk. The use of large-scale methods to identify and characterize genetic material (i.e., high-throughput technologies) for data gathering and analysis recently has made it possible to investigate the complexity of the genetic architecture of susceptibility to common diseases such as alcoholism on a systems level. Systems genetics is the study of all genetic variations, their interactions with each other (i.e., epistasis), their interactions with the environment (i.e., plastic reaction norms), their relationship with interindividual variation in traits that are influenced by many genes and contribute to disease susceptibility (i.e., intermediate quantitative traits or endophenotypes) defined at different levels of hierarchical biochemical and physiological systems, and their relationship with health and disease. (An endophenotype is a genetically determined trait [i.e., phenotype] that is not immediately visible but may contribute to the susceptibility to develop a particular behavior or syndrome. See the glossary, p. 84, for descriptions of other technical terms used in this article.) The goal of systems genetics is to provide an understanding of the complex relationship between the genome and disease by investigating intermediate biological processes. After investigating main effects, the first step in a systems genetics approach, as described here, is to search for gene-gene (i.e., epistatic) reactions.

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The contribution of genes to alcoholism progresses through a hierarchy of gene expression, protein interaction, and physiology within the context of environment. Though association, linkage, expression, proteomic, physiological, and environmental studies capture pertinent information from each hierarchical level, they do not independently capture the complex interaction actually responsible for disease. Colored shapes represent interacting gene products (i.e., RNA and proteins).
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f3-arh-31-1-14: The contribution of genes to alcoholism progresses through a hierarchy of gene expression, protein interaction, and physiology within the context of environment. Though association, linkage, expression, proteomic, physiological, and environmental studies capture pertinent information from each hierarchical level, they do not independently capture the complex interaction actually responsible for disease. Colored shapes represent interacting gene products (i.e., RNA and proteins).

Mentions: Documenting the role of epistasis in alcoholism as described above is a good first step toward thinking about how genes work together to influence risk. However, a more complete understanding of the hierarchical mapping relationship between genotype and phenotype will come from studying other key biomolecules, such as mRNA and proteins, and their interactions. The ultimate goal of systems genetics is to determine how these biomolecular interactions in a particular ecological context influence the physiological processes that are responsible for disease phenotypes (figure 3). This information will dramatically increase our ability to develop effective prevention and treatment strategies. The studies and strategies reviewed below provide a basis for moving forward with a systems genetics approach to alcoholism.


Systems genetics of alcoholism.

Sloan CD, Sayarath V, Moore JH - Alcohol Res Health (2008)

The contribution of genes to alcoholism progresses through a hierarchy of gene expression, protein interaction, and physiology within the context of environment. Though association, linkage, expression, proteomic, physiological, and environmental studies capture pertinent information from each hierarchical level, they do not independently capture the complex interaction actually responsible for disease. Colored shapes represent interacting gene products (i.e., RNA and proteins).
© Copyright Policy - public-domain
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3860445&req=5

f3-arh-31-1-14: The contribution of genes to alcoholism progresses through a hierarchy of gene expression, protein interaction, and physiology within the context of environment. Though association, linkage, expression, proteomic, physiological, and environmental studies capture pertinent information from each hierarchical level, they do not independently capture the complex interaction actually responsible for disease. Colored shapes represent interacting gene products (i.e., RNA and proteins).
Mentions: Documenting the role of epistasis in alcoholism as described above is a good first step toward thinking about how genes work together to influence risk. However, a more complete understanding of the hierarchical mapping relationship between genotype and phenotype will come from studying other key biomolecules, such as mRNA and proteins, and their interactions. The ultimate goal of systems genetics is to determine how these biomolecular interactions in a particular ecological context influence the physiological processes that are responsible for disease phenotypes (figure 3). This information will dramatically increase our ability to develop effective prevention and treatment strategies. The studies and strategies reviewed below provide a basis for moving forward with a systems genetics approach to alcoholism.

Bottom Line: Systems genetics is the study of all genetic variations, their interactions with each other (i.e., epistasis), their interactions with the environment (i.e., plastic reaction norms), their relationship with interindividual variation in traits that are influenced by many genes and contribute to disease susceptibility (i.e., intermediate quantitative traits or endophenotypes) defined at different levels of hierarchical biochemical and physiological systems, and their relationship with health and disease. (An endophenotype is a genetically determined trait [i.e., phenotype] that is not immediately visible but may contribute to the susceptibility to develop a particular behavior or syndrome.See the glossary, p. 84, for descriptions of other technical terms used in this article.) The goal of systems genetics is to provide an understanding of the complex relationship between the genome and disease by investigating intermediate biological processes.After investigating main effects, the first step in a systems genetics approach, as described here, is to search for gene-gene (i.e., epistatic) reactions.

View Article: PubMed Central - PubMed

Affiliation: Section of Epidemiology and Biostatistics, Department of Community and Family Medicine, Dartmouth Medical School, Lebanon, New Hampshire.

ABSTRACT
Alcoholism is a common disease resulting from the complex interaction of genetic, social, and environmental factors. Interest in the high heritability of alcoholism has resulted in many studies of how single genes, as well as an individual's entire genetic content (i.e., genome) and the proteins expressed by the genome, influence alcoholism risk. The use of large-scale methods to identify and characterize genetic material (i.e., high-throughput technologies) for data gathering and analysis recently has made it possible to investigate the complexity of the genetic architecture of susceptibility to common diseases such as alcoholism on a systems level. Systems genetics is the study of all genetic variations, their interactions with each other (i.e., epistasis), their interactions with the environment (i.e., plastic reaction norms), their relationship with interindividual variation in traits that are influenced by many genes and contribute to disease susceptibility (i.e., intermediate quantitative traits or endophenotypes) defined at different levels of hierarchical biochemical and physiological systems, and their relationship with health and disease. (An endophenotype is a genetically determined trait [i.e., phenotype] that is not immediately visible but may contribute to the susceptibility to develop a particular behavior or syndrome. See the glossary, p. 84, for descriptions of other technical terms used in this article.) The goal of systems genetics is to provide an understanding of the complex relationship between the genome and disease by investigating intermediate biological processes. After investigating main effects, the first step in a systems genetics approach, as described here, is to search for gene-gene (i.e., epistatic) reactions.

Show MeSH
Related in: MedlinePlus