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Genetic factors

Genetic factors, along with socio -environmental (e.g., psychosocial) factors, have been established as significant contributors to addiction vulnerability. Studies done on 350 hospitalized drug-dependent patients showed that over half met the criteria for alcohol abuse, with a role of familial factors being prevalent. Genetic factors account for 40–60% of the risk factors for alcoholism. Similar rates of heritability for other types of drug addiction have been indicated, specifically in genes that encode the Alpha5 Nicotinic Acetylcholine Receptor. Knestler hypothesized in 1964 that a gene or group of genes might contribute to predisposition to addiction in several ways. For example, altered levels of a normal protein due to environmental factors may change the structure or functioning of specific brain neurons during development. These altered brain neurons could affect the susceptibility of an individual to an initial drug use experience. In support of this hypothesis, animal studies have shown that environmental factors such as stress can affect an animal's genetic expression.

In humans, twin studies into addiction have provided some of the highest-quality evidence of this link, with results finding that if one twin is affected by addiction, the other twin is likely to be as well, and to the same substance. Further evidence of a genetic component is research findings from family studies which suggest that if one family member has a history of addiction, the chances of a relative or close family developing those same habits are much higher than one who has not been introduced to addiction at a young age.

The data implicating specific genes in the development of drug addiction is mixed for most genes. Many addiction studies that aim to identify specific genes focus on common variants with an allele frequency of greater than 5% in the general population. When associated with disease, these only confer a small amount of additional risk with an odds ratio of 1.1–1.3 percent; this has led to the development the rare variant hypothesis, which states that genes with low frequencies in the population (<1%) confer much greater additional risk in the development of the disease.

Genome-wide association studies (GWAS) are used to examine genetic associations with dependence, addiction, and drug use. These studies rarely identify genes from proteins previously described via animal knockout models and candidate gene analysis. Instead, large percentages of genes involved in processes such as cell adhesion are commonly identified. The important effects of endophenotypes are typically not capable of being captured by these methods. Genes identified in GWAS for drug addiction may be involved either in adjusting brain behavior before drug experiences, subsequent to them, or both.