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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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Related in: MedlinePlus

Multifactor dimensionality reduction (MDR) attribute construction. A) Distribution of cases (left bars) and controls (right bars) for each of the three genotypes of single nucleotide polymorphism (SNP) 1 and SNP2. The dark-shaded cells have been labeled “high risk,” and the light-shaded cells have been labeled “low risk.” B) Distribution of cases and controls when the two functional SNPs are considered jointly. A new single attribute is constructed by pooling the high-risk genotype combinations into one group (G1) and the low-risk genotype into another group (G0).
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f2-arh-31-1-14: Multifactor dimensionality reduction (MDR) attribute construction. A) Distribution of cases (left bars) and controls (right bars) for each of the three genotypes of single nucleotide polymorphism (SNP) 1 and SNP2. The dark-shaded cells have been labeled “high risk,” and the light-shaded cells have been labeled “low risk.” B) Distribution of cases and controls when the two functional SNPs are considered jointly. A new single attribute is constructed by pooling the high-risk genotype combinations into one group (G1) and the low-risk genotype into another group (G0).

Mentions: Constructive induction using MDR is accomplished in the following way. Given a threshold T, a multilocus genotype combination is considered high risk if the ratio of cases (subjects with disease) to controls (healthy subjects) exceeds T; otherwise, it is considered low risk. Genotype combinations considered to be high risk are labeled G1, whereas those considered low risk are labeled G0. This process constructs a new one-dimensional attribute with levels G0 and G1. It is this new single variable that is assessed using a classification method such as naïve Bayes7 or logistic regression. Figure 2 illustrates the constructive induction process used in MDR for two interacting SNPs.


Systems genetics of alcoholism.

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

Multifactor dimensionality reduction (MDR) attribute construction. A) Distribution of cases (left bars) and controls (right bars) for each of the three genotypes of single nucleotide polymorphism (SNP) 1 and SNP2. The dark-shaded cells have been labeled “high risk,” and the light-shaded cells have been labeled “low risk.” B) Distribution of cases and controls when the two functional SNPs are considered jointly. A new single attribute is constructed by pooling the high-risk genotype combinations into one group (G1) and the low-risk genotype into another group (G0).
© Copyright Policy - public-domain
Related In: Results  -  Collection

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

f2-arh-31-1-14: Multifactor dimensionality reduction (MDR) attribute construction. A) Distribution of cases (left bars) and controls (right bars) for each of the three genotypes of single nucleotide polymorphism (SNP) 1 and SNP2. The dark-shaded cells have been labeled “high risk,” and the light-shaded cells have been labeled “low risk.” B) Distribution of cases and controls when the two functional SNPs are considered jointly. A new single attribute is constructed by pooling the high-risk genotype combinations into one group (G1) and the low-risk genotype into another group (G0).
Mentions: Constructive induction using MDR is accomplished in the following way. Given a threshold T, a multilocus genotype combination is considered high risk if the ratio of cases (subjects with disease) to controls (healthy subjects) exceeds T; otherwise, it is considered low risk. Genotype combinations considered to be high risk are labeled G1, whereas those considered low risk are labeled G0. This process constructs a new one-dimensional attribute with levels G0 and G1. It is this new single variable that is assessed using a classification method such as naïve Bayes7 or logistic regression. Figure 2 illustrates the constructive induction process used in MDR for two interacting SNPs.

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