Is Alcoholism Hereditary or Genetic?

After years of family-based linkage studies and case-control candidate gene studies, attention has shifted to large scale genome-wide association studies (GWAS) for the detection of novel common variants (≥ 1%). Exome and whole genome sequencing studies for the detection of rare variants are beginning to emerge. However, it should be borne in mind that no matter how sophisticated Genetics of Alcoholism genetic techniques might become, further advances in detecting genotype – phenotype associations are hampered by the fact that alcoholism is a heterogeneous phenotype. One way around this has been the use of intermediate phenotypes, including electrophysiological and imaging, that reflect mediating factors in behavior and are likely to be influenced by variation at fewer genes.

RECRUITMENT: A FOCUS ON FAMILIES

• The Centers for Disease Control and Prevention (CDC) has reported that alcohol use contributes to approximately 88,000 deaths annually in the United States (Stahre et al., 2014), reflecting high morbidity and mortality.
• Yet fewer than 1 in 4 classified as requiring addiction treatment received medical care relating to their substance use.
• It also is essential that the provider tailor treatment, which may include behavioral therapies and medications, to an individual’s specific combination of disorders and symptoms.

Therefore, heart rate and acetaldehyde levels after alcohol consumption can provide biomarkers in humans to understand individual genetic differences in alcohol metabolism. Vrieze et al. (2013) found that, in biometric twin models, behavioral inhibition was highly genetically correlated with all substance use traits (nicotine use/dependence, alcohol consumption, alcohol dependence, and drug use). Regarding alcohol dependence, heritability was as high as 56%, and the aggregate additive SNP effects estimated by GCTA on the parent sample accounted for 16% of the variance (Vrieze et al., 2013). Hence, Vrieze et al. (2013) found that substance use phenotypes, including those pertaining to alcohol use, and behavioral disinhibition share a genetic etiology, and that measured genetic variants contribute to their heritability. A changing definition of the heterogeneous phenotype of AUD may also pose a challenge to identifying genetic variants through GWAS. The above studies used the DSM-IV-TR criteria for alcohol dependence in order to define the phenotype.

Topic Series: Update on the Genetics of Alcoholism

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• Reassuringly, many COGA findings have been replicated in other samples (e.g., References 76, 77, 78, 79).
• In addition, NIAAA funds investigators’ research in this important field, and also has an in-house research emphasis on the interaction of genes and the environment.
• “Substance use disorders and mental disorders often co-occur, and we know that the most effective treatments help people address both issues at the same time.
• More than 800,000 of the people affected are children between the ages of 12 and 17 years.

Of note, assessments, interviewer training and data cleaning are standardized across all sites, with some variations in assessment driven by individual institutional IRB criteria. Taken together, these waves of longitudinal follow‐up provide a perspective of AUD risk and resilience across the lifespan. Analyses of 987 people from 105 families in the initial sample provided evidence that regions on 3 chromosomes contained genes that increase the risk for alcoholism (Reich et al. 1998).

• Alcohol is metabolized primarily in the liver, although thereis some metabolism in the upper GI tract and stomach.
• These groups typically have a lower risk of developing alcohol use disorder compared to other populations.
• The breath metabolite acetaldehyde was measured from a Tedlar bag using selective ion flow mass spectrometry (Syft Voice Ultra, New Zealand).
• While the recent use of GWAS to identify the underlying genetic components of AUD has been promising, there are several limitations of GWAS that must be considered.

What gene is responsible for increased AUD risk?

Analysis of such electrophysiological data may reveal a subset of genes that affect these quantitative, biological phenotypes related to alcoholism (Porjesz et al. 1998, 2002). One component of an ERP is a brain wave called P300, which typically occurs 300 milliseconds after a stimulus. Previous studies had found that a reduced amplitude of the P300 wave is a heritable phenotype that correlates with alcohol dependence and other psychiatric disorders (Porjesz et al. 1998). https://ecosoberhouse.com/ The genetic analyses of the COGA participants identified four regions, on chromosomes 2, 5, 6, and 13, that appear to contain genes affecting the amplitude of the P300 (Begleiter et al. 1998). COGA ascertained probands in treatment for alcohol dependence, and a smaller number of comparison individuals from the same communities, and then recruited their families. Approximately 75% of the families were ascertained via a proband in treatment for alcohol dependence.

Extended Data Fig. 3 Phenome-wide associations with PAU PRS in PsycheMERGE EUR samples.

Environmental factors of alcohol use disorder

The Role of the National Institute on Alcohol Abuse and Alcoholism (NIAAA)

• We have since conducted several studies that have disentangled family history into elements of genetic liability, nurture and density of risk (e.g., References 23, 24, 25).
• In children aged 9 or 10 years without any experience of substance use, these genes correlated with parental substance use and externalizing behavior.
• We published a comprehensive review of the genetics of alcoholism over a decade ago [1].
• Furthermore, whole genome sequencing (WGS) methods, especially as their accessibility increases, would substantively improve COGA’s ability to study rarer and structural variants, the role of which continues to emerge for psychiatric disorders.
• The genomic pattern linked to general addiction risk also predicted higher risk of mental and physical illness, including psychiatric disorders, suicidal behavior, respiratory disease, heart disease, and chronic pain conditions.