Genetic influences on the development of alcoholism.
paper
Cited
Public
- Authors
- Enoch, Mary-Anne
- Year
- 2013
- Journal
- Current psychiatry reports
- PMID
- 24091936
- DOI
- 10.1007/s11920-013-0412-1
- PMCID
- PMC4159132
Alcoholism has a substantial heritability yet the detection of specific genetic influences has largely proved elusive. The strongest findings are with genes encoding alcohol metabolizing enzymes. A few candidate genes such as GABRA2 have shown robust associations with alcoholism. Moreover, it has become apparent that variants in stress-related genes such as CRHR1, may only confer risk in individuals exposed to trauma, particularly in early life. Over the past decade there have been tremendous advances in large scale SNP genotyping technologies allowing for genome-wide associations studies (GWAS). As a result, it is now recognized that genetic risk for alcoholism is likely to be due to common variants in very many genes, each of small effect, although rare variants with large effects might also play a role. This has resulted in a paradigm shift away from gene centric studies toward analyses of gene interactions and gene networks within biologically relevant pathways.
Stress-Addictions ArrayThis is an illustration of an Illumina GoldenGate array that was custom designed to include 1350 haplotype tagging single nucleotide polymorphisms (SNPs) within 127 stress- and addictions-related genes. This array was designed for Caucasian and African ancestry, hence the limited number of alcohol metabolism genes. The array also includes 186 ancestry informative markers.
LLM interpretation
This figure is a conceptual diagram illustrating the design of a custom Illumina GoldenGate array. A central circle indicates the array contains 1350 SNPs across 127 genes, with arrows pointing to categorized lists of specific genes. These categories include Stress, Cholinergic, Adrenergic, Other, Drug Metabolism, Dopamine, Serotonin, GABA, Opioid, Glycine, Glutamate, Cannabinoid, and Signal Transduction.
| # | Section | Preview |
|---|---|---|
| 20 | STRATEGIES FOR IDENTIFYING GENETIC ASSOCIATIONS WITH ALCOHOLISM β The βEducated Guessβ Approach β Candidate Genes on Arrays | As yet, no GABRA2 functional variant has been detected to explain the yin yang haplotype (or tagβ¦ |
| 21 | STRATEGIES FOR IDENTIFYING GENETIC ASSOCIATIONS WITH ALCOHOLISM β Gene-Gene Effects within Biological Pathways | Biologically relevant combinations of functional variants within gene networks are likely to haveβ¦ |
| 22 | STRATEGIES FOR IDENTIFYING GENETIC ASSOCIATIONS WITH ALCOHOLISM β Gene-Gene Effects within Biological Pathways | HTR3A and HTR3B that increased risk for AUD [56] and predicted the response of alcoholics to theβ¦ |
| 23 | STRATEGIES FOR IDENTIFYING GENETIC ASSOCIATIONS WITH ALCOHOLISM β Gene x Environment Interactive Effects on Risk for Alcoholism | The experience of maltreatment and cumulative stressful life events prior to puberty andβ¦ |
| 24 | STRATEGIES FOR IDENTIFYING GENETIC ASSOCIATIONS WITH ALCOHOLISM β Genome-wide Association Studies (GWAS) | GWAS have no a priori hypothesis but ask whether a phenotype might be associated with any of a veryβ¦ |
| 25 | STRATEGIES FOR IDENTIFYING GENETIC ASSOCIATIONS WITH ALCOHOLISM β Genome-wide Association Studies (GWAS) | The strongest and most consistent findings for GWAS for AUD are for alcohol metabolizing genes, asβ¦ |
| 26 | STRATEGIES FOR IDENTIFYING GENETIC ASSOCIATIONS WITH ALCOHOLISM β Genome-wide Association Studies (GWAS) | Other major findings from GWAS for AUD, alcohol-related phenotypes and comorbid diseases are listedβ¦ |
| 27 | STRATEGIES FOR IDENTIFYING GENETIC ASSOCIATIONS WITH ALCOHOLISM β Genome-wide Association Studies (GWAS) | One of the earlier GWAS of AUD illustrates the kinds of manipulations that are being undertaken inβ¦ |
| 28 | STRATEGIES FOR IDENTIFYING GENETIC ASSOCIATIONS WITH ALCOHOLISM β Genome-wide Association Studies (GWAS) | GWAS in 2600 individuals derived from the Study of Addiction: Genes and Environment (SAGE) dataset.β¦ |
| 29 | STRATEGIES FOR IDENTIFYING GENETIC ASSOCIATIONS WITH ALCOHOLISM β Genome-wide Association Studies (GWAS) | Innovative statistical approaches are being pioneered to make biological sense out of GWAS data.β¦ |
| 30 | STRATEGIES FOR IDENTIFYING GENETIC ASSOCIATIONS WITH ALCOHOLISM β Genome-wide Association Studies (GWAS) | As discussed above, few robust associations between specific gene variants and complex behaviorsβ¦ |
| 31 | STRATEGIES FOR IDENTIFYING GENETIC ASSOCIATIONS WITH ALCOHOLISM β Genome-wide Association Studies (GWAS) | Awareness of the need for large sample sizes for GWAS has resulted in the formation of large scaleβ¦ |
| 32 | STRATEGIES FOR IDENTIFYING GENETIC ASSOCIATIONS WITH ALCOHOLISM β Genome-wide Association Studies (GWAS) | One way of bypassing the sample size issue is to study intermediate phenotypes in populationβ¦ |
| 33 | STRATEGIES FOR IDENTIFYING GENETIC ASSOCIATIONS WITH ALCOHOLISM β Direct Sequencing of Rare Variants | Some researchers have hypothesized that there may be large panels of rare functional variants, eachβ¦ |
| 34 | CONCLUSIONS | Alcoholism is known to be moderately heritable yet the search for genetic vulnerability factors has⦠|
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