The genetic basis of alcoholism: multiple phenotypes, many genes, complex networks Full Text

In higher organisms, including humans, the genes encoding the various components of the body are not just simple stretches of DNA that serve as a template from which proteins are generated. Instead, they have a complex structure involving, in some cases, dozens of pieces of coding sequences interspersed with noncoding sequences. The coding sequences, which are those parts of the gene that actually serve as templates for protein production, are called exons. In addition to the exons and introns, genes contain regulatory sequences that determine in which cell, at what time, and in what amount the gene is actively converted into the corresponding protein (i.e., is expressed).

Genetic Influences on Alcohol Metabolism

In addition, 9871 individuals have brain function data from electroencephalogram (EEG) recordings while 12,009 individuals have been genotyped on genome‐wide association study (GWAS) arrays. A series of functional genomics studies examine the specific cellular and molecular mechanisms underlying AUD. This overview provides the framework for the development of COGA as a scientific resource in the past three decades, with individual reviews providing in‐depth descriptions of data on and discoveries from behavioral and clinical, brain function, genetic and functional genomics data. Environmental factors such as family and social influences, availability of alcohol, and overall lifestyle choices can greatly affect an individual’s likelihood of developing alcoholism. Research suggests that individuals with a genetic predisposition to alcoholism may be more susceptible to the negative effects of these environmental factors, leading to an increased risk of developing the disease.

Links to NCBI Databases

• Alpha synuclein (SNCA) is a gene that maps to a QTL for alcohol preference, and expression of alpha synuclein is increased in different brain areas in rats displaying alcohol preference 126.
• Understanding how epigenetic modifications contribute to alcoholism can provide valuable insights into the development of targeted treatments and prevention strategies.
• Research has shown that individuals with a family history of alcoholism have a higher risk of developing alcoholism themselves.
• Qualified investigators can access freely available GWAS datasets via the database of Genotypes and Phenotypes (dbGaP) 83 and several studies have used this resource for replication samples.

Another approach that has been proposed is to use stratified False Discovery Rate methods to uncover new loci likely to replicate in independent samples. One recent study has demonstrated enrichment of polygenic effects, particularly for SNPs tagging regulatory and coding genic elements 78. For example, a study https://ecosoberhouse.com/ in 33,332 patients and 27,888 controls used a combination of polygenic risk score analyses and pathway analyses to support a role for calcium channel signaling genes across five psychiatric disorders 79.

Transancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders

This is an illustration of an Illumina GoldenGate array that was custom designed to include 1350 haplotype tagging single nucleotide polymorphisms (SNPs) within 127 genetic disposition to alcoholism stress- and addictions-related genes. This array was designed for Caucasian and African ancestry, hence the limited number of alcohol metabolism genes. The transition to addiction involves multiple neuroadaptations and much of our understanding of these processes has so far been obtained from animal studies. However the use of microarrays and advances in next-generation RNA-sequencing (RNA-Seq) 35 have conferred the ability to quantify mRNA transcripts in postmortem brain and analyze expression differences between alcoholics and controls within gene networks 36–39.

• Among all SNPs that were significant at a nominal P-value in the studies described above, the gene encoding cadherin 13 (CDH13) was replicated in four independent studies, and eight genes were common across any three studies (Table 1).
• In the context of alcoholism, pharmacogenetics plays a crucial role in the development of personalized treatment strategies.
• Innovations are required at the analytical level to integrate and validate the massive amounts of data produced by these new technologies and different approaches.
• A model of genetic determinism in which different alleles lead to the same phenotype in different individuals, but an individual allele can suffice to produce the phenotype.
• Furthermore, noncoding variations in various alcohol-metabolizing enzymes likely also affect risk for alcoholism (Edenberg et al. 2006).

This is conducted by looking at the cross-inheritance of different diseases within families and in twin pairs. Twin and family studies on alcoholism have revealed that genetic factors acting on alcoholism Drug rehabilitation include both alcohol-specific genetic factors as well as genetic factors that are shared with other addictions (for review see Goldman & Bergen) 8. For example, results from several twin studies 9-13 have detected consistently a considerable overlap in the genetic liability to alcoholism and nicotine dependence, particularly in individuals who drink or smoke heavily.