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Assessing the genetic risk for alcohol use disorders.

Foroud T, Phillips TJ - Alcohol Res (2012)

Bottom Line: The past two decades have witnessed a revolution in the field of genetics which has led to a rapid evolution in the tools and techniques available for mapping genes that contribute to genetically complex disorders such as alcohol dependence.Research in humans and in animal models of human disease has provided important new information.All of these approaches have led to the identification of several genes that seem to influence the risk for alcohol dependence, which are being further analyzed.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana.

ABSTRACT
The past two decades have witnessed a revolution in the field of genetics which has led to a rapid evolution in the tools and techniques available for mapping genes that contribute to genetically complex disorders such as alcohol dependence. Research in humans and in animal models of human disease has provided important new information. Among the most commonly applied approaches used in human studies are family studies, case-control studies, and genome-wide association studies. Animal models have been aimed at identifying genetic regions or individual genes involved in different aspects of alcoholism, using such approaches as quantitative trait locus analysis, genome sequencing, knockout animals, and other sophisticated molecular genetic techniques. All of these approaches have led to the identification of several genes that seem to influence the risk for alcohol dependence, which are being further analyzed. Newer studies, however, also are attempting to look at the genetic basis of alcoholism at the level of the entire genome, moving beyond the study of individual genes toward analyses of gene interactions and gene networks in the development of this devastating disease.

No MeSH data available.


Related in: MedlinePlus

Strategies to identify genes contributing to alcohol dependence. A) Family study. In this figure, the squares represent males; the circles, females. The individuals with lines connecting their symbols produced children together and the lines down from that pair of individuals depict their offspring. Fully shaded symbols indicate individuals in the family who are alcohol dependent. The bars beside each symbol represent a region in the genome. Each individual has two copies of this region (one inherited from their mother and one from their father). The black bar carries a version of the gene (i.e., an allele) with a variation in its sequence that increases the risk of alcoholism. Notice that in this family, all four alcoholic individuals carry one copy of the allele that increases the alcoholism risk. The individuals who are not alcohol dependent do not carry this allele. If this pattern is repeated across many families, then there is likely to be a gene that influences the risk for alcoholism in this part of the genome. B) Case–control study. The three colors represent the three possible genetic makeups (i.e., genotypes) at the marker. The cases have more individuals with the green genotype and fewer with the blue genotype, whereas the controls have more individuals with the blue genotype and fewer with the green, suggesting that the green genotype is associated with an increased risk for alcohol dependence.
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f1-arcr-34-3-266: Strategies to identify genes contributing to alcohol dependence. A) Family study. In this figure, the squares represent males; the circles, females. The individuals with lines connecting their symbols produced children together and the lines down from that pair of individuals depict their offspring. Fully shaded symbols indicate individuals in the family who are alcohol dependent. The bars beside each symbol represent a region in the genome. Each individual has two copies of this region (one inherited from their mother and one from their father). The black bar carries a version of the gene (i.e., an allele) with a variation in its sequence that increases the risk of alcoholism. Notice that in this family, all four alcoholic individuals carry one copy of the allele that increases the alcoholism risk. The individuals who are not alcohol dependent do not carry this allele. If this pattern is repeated across many families, then there is likely to be a gene that influences the risk for alcoholism in this part of the genome. B) Case–control study. The three colors represent the three possible genetic makeups (i.e., genotypes) at the marker. The cases have more individuals with the green genotype and fewer with the blue genotype, whereas the controls have more individuals with the blue genotype and fewer with the green, suggesting that the green genotype is associated with an increased risk for alcohol dependence.

Mentions: In human studies, several strategies have been used to search for the genes that influence complex traits such as alcohol dependence, which are influenced by multiple genes with smaller effects rather than by one or more genes with larger effect sizes (Edenberg and Foroud 2006; also see the article by Agrawal and Bierut, pp. 274–282). One approach, often termed linkage analysis, involves studying families with multiple members who have alcohol dependence. This approach is based on the hypothesis that genes might have a greater effect in these families than in families with only a single alcoholic member. To perform this type of study, researchers recruited hundreds of families having two or more alcoholic members (see figure 1A) and analyzed DNA samples from both alcoholic and nonalcoholic family members at approximately 400 different positions within the human genome for sequence differences. The data then were examined to determine whether alcohol-dependent individuals within families shared common gene variants (i.e., alleles). Finally, the investigators reviewed the data across all families in a study to determine whether individuals with alcoholism seemed to have inherited particular parts of the genome. Those portions of the genome that seem to be shared are called quantitative trait loci (QTLs) and are hypothesized to include genes that contribute to the risk for alcoholism. The QTLs can be quite large, often covering 10 or 20 million base pairs that may include hundreds or even thousands of genes, of which the right one or ones (because more than one in the region could contribute) would need to be identified. Although this approach was quite challenging, investigators were able to locate several genome regions that are thought to include genes that contribute to the risk for alcohol dependence. However, conclusively identifying the relevant gene(s) from the many within each large region has proven to be more difficult than anticipated.


Assessing the genetic risk for alcohol use disorders.

Foroud T, Phillips TJ - Alcohol Res (2012)

Strategies to identify genes contributing to alcohol dependence. A) Family study. In this figure, the squares represent males; the circles, females. The individuals with lines connecting their symbols produced children together and the lines down from that pair of individuals depict their offspring. Fully shaded symbols indicate individuals in the family who are alcohol dependent. The bars beside each symbol represent a region in the genome. Each individual has two copies of this region (one inherited from their mother and one from their father). The black bar carries a version of the gene (i.e., an allele) with a variation in its sequence that increases the risk of alcoholism. Notice that in this family, all four alcoholic individuals carry one copy of the allele that increases the alcoholism risk. The individuals who are not alcohol dependent do not carry this allele. If this pattern is repeated across many families, then there is likely to be a gene that influences the risk for alcoholism in this part of the genome. B) Case–control study. The three colors represent the three possible genetic makeups (i.e., genotypes) at the marker. The cases have more individuals with the green genotype and fewer with the blue genotype, whereas the controls have more individuals with the blue genotype and fewer with the green, suggesting that the green genotype is associated with an increased risk for alcohol dependence.
© Copyright Policy - public-domain
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3860406&req=5

f1-arcr-34-3-266: Strategies to identify genes contributing to alcohol dependence. A) Family study. In this figure, the squares represent males; the circles, females. The individuals with lines connecting their symbols produced children together and the lines down from that pair of individuals depict their offspring. Fully shaded symbols indicate individuals in the family who are alcohol dependent. The bars beside each symbol represent a region in the genome. Each individual has two copies of this region (one inherited from their mother and one from their father). The black bar carries a version of the gene (i.e., an allele) with a variation in its sequence that increases the risk of alcoholism. Notice that in this family, all four alcoholic individuals carry one copy of the allele that increases the alcoholism risk. The individuals who are not alcohol dependent do not carry this allele. If this pattern is repeated across many families, then there is likely to be a gene that influences the risk for alcoholism in this part of the genome. B) Case–control study. The three colors represent the three possible genetic makeups (i.e., genotypes) at the marker. The cases have more individuals with the green genotype and fewer with the blue genotype, whereas the controls have more individuals with the blue genotype and fewer with the green, suggesting that the green genotype is associated with an increased risk for alcohol dependence.
Mentions: In human studies, several strategies have been used to search for the genes that influence complex traits such as alcohol dependence, which are influenced by multiple genes with smaller effects rather than by one or more genes with larger effect sizes (Edenberg and Foroud 2006; also see the article by Agrawal and Bierut, pp. 274–282). One approach, often termed linkage analysis, involves studying families with multiple members who have alcohol dependence. This approach is based on the hypothesis that genes might have a greater effect in these families than in families with only a single alcoholic member. To perform this type of study, researchers recruited hundreds of families having two or more alcoholic members (see figure 1A) and analyzed DNA samples from both alcoholic and nonalcoholic family members at approximately 400 different positions within the human genome for sequence differences. The data then were examined to determine whether alcohol-dependent individuals within families shared common gene variants (i.e., alleles). Finally, the investigators reviewed the data across all families in a study to determine whether individuals with alcoholism seemed to have inherited particular parts of the genome. Those portions of the genome that seem to be shared are called quantitative trait loci (QTLs) and are hypothesized to include genes that contribute to the risk for alcoholism. The QTLs can be quite large, often covering 10 or 20 million base pairs that may include hundreds or even thousands of genes, of which the right one or ones (because more than one in the region could contribute) would need to be identified. Although this approach was quite challenging, investigators were able to locate several genome regions that are thought to include genes that contribute to the risk for alcohol dependence. However, conclusively identifying the relevant gene(s) from the many within each large region has proven to be more difficult than anticipated.

Bottom Line: The past two decades have witnessed a revolution in the field of genetics which has led to a rapid evolution in the tools and techniques available for mapping genes that contribute to genetically complex disorders such as alcohol dependence.Research in humans and in animal models of human disease has provided important new information.All of these approaches have led to the identification of several genes that seem to influence the risk for alcohol dependence, which are being further analyzed.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana.

ABSTRACT
The past two decades have witnessed a revolution in the field of genetics which has led to a rapid evolution in the tools and techniques available for mapping genes that contribute to genetically complex disorders such as alcohol dependence. Research in humans and in animal models of human disease has provided important new information. Among the most commonly applied approaches used in human studies are family studies, case-control studies, and genome-wide association studies. Animal models have been aimed at identifying genetic regions or individual genes involved in different aspects of alcoholism, using such approaches as quantitative trait locus analysis, genome sequencing, knockout animals, and other sophisticated molecular genetic techniques. All of these approaches have led to the identification of several genes that seem to influence the risk for alcohol dependence, which are being further analyzed. Newer studies, however, also are attempting to look at the genetic basis of alcoholism at the level of the entire genome, moving beyond the study of individual genes toward analyses of gene interactions and gene networks in the development of this devastating disease.

No MeSH data available.


Related in: MedlinePlus