Seeking the Connections: Alcoholism and Our Genes
One recent study has demonstrated enrichment of polygenic effects, particularly for SNPs tagging regulatory and coding genic elements 78. For example, a study 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. The reanalysis reviewed here has confirmed the consistency of the evidence for an important genetic influence on alcoholism risk from both twin and adoption studies. Many studies that followed children of alcoholics prospectively to identify precursors of alcoholism risk have focused on sons of alcoholics, assuming a stronger genetic influence in men than in women (for further discussion of markers, see the article by Anthenelli and Tabakoff, pp. 176–181). This assumption does not appear to be supported by the data, at least for the definitions of alcoholism analyzed here. Many genes contribute to this risk, with most of those genes making only very small contributions to the overall risk.
For participants from families with three or more alcoholic family members, the investigators conducted genetic analyses using microsatellite markers—DNA regions located across all chromosomes, in which short repeated sequences exist in many variants (i.e., alleles). More than 1.2 million genotypes have been generated on 2,310 people from families of alcoholics and 1,238 people from control families. By monitoring the inheritance patterns of such marker alleles within families with alcoholic members, the investigators could identify chromosomal regions that influence (i.e., show genetic linkage with) certain alcohol-related traits. Family studies have consistently demonstrated that there is a substantialgenetic contribution to alcohol dependence. Extensive study of the alcoholmetabolizing genes has demonstrated their important role in disease risk. Additionalgenes have been identified that have expanded our understanding of the genes andpathways involved; however, the number of findings to date is modest.
Other Addictive Behavior
Although most of the genetic determinants of alcoholism remain to be discovered there are reasons for optimism. In recent years a technological revolution has occurred producing a shift from single-locus studies to genome-wide searches. The genomes trascriptome, epigenome and, to some extent, proteome, can now be assessed at a level of detail that was previously inconceivable.
Thus, a gene or genes that affect brain rhythms lies in a region of chromosome 4 that contains a cluster of genes encoding proteins (i.e., receptors) which interact with the brain chemical gamma-aminobutyric acid (GABA). This is relatively small in comparison to schizophrenia, where genetics can explain eighty percent of the disease predisposition. Therefore, as research progresses, consideration must still be made for the environment—the “nurture”—that individuals were raised and live in. We need to spend more time in gene discovery before bringing it into patient care,” Zhou said. As it turns out, there is no “alcoholic” gene in the human genome, nor is there an absolute “AUD-causing” environment or situation.
- Living in a household where you’re regularly exposed to parental alcohol use can also increase your chances of AUD, regardless of your genetic predisposition.
- Take our free, 5-minute alcohol abuse self-assessment below if you think you or someone you love might be struggling with substance abuse.
- Therefore, the increased sensitivity to adverse experiences of carriers of the low activity MAOA genotype might be due to their impaired ability to extinguish adverse memories and conditioned fears.
Therefore, additional markers within these regions of interest were analyzed in the same people. Subsequent analyses that included the additional markers supported the initial findings (Foroud et al. 2000) but did not narrow the chromosomal regions in which genes influencing alcoholism susceptibility are likely to lie. The investigators chose a family study design to allow the use of multiple methods of genetic analysis. Systematic recruitment from outpatient and inpatient alcoholism treatment facilities and assessment of can police dogs smell nicotine vapes families initially was carried out at six sites across the United States, with a seventh site more recently. The study also included a large sample of control families that were randomly selected from the community. For the analyses, the researchers chose a split-sample design—two groups of subjects (i.e., an initial sample and a replication sample) were analyzed independently; this approach allows investigators to examine the reproducibility of the initial study findings.
GENETICS DATA
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). 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). Alcohol is widely consumed, but excessive use creates serious physical,psychological and social problems and contributes to many diseases. Alcoholism(alcohol dependence, alcohol use disorders) is a maladaptive pattern ofexcessive drinking leading to serious problems.
Is Alcoholism Genetic? Understanding the Genetics of Alcoholism
In 1990, Blum et al. proposed an association between the A1 allele of the DRD2 gene and alcoholism. The DRD2 gene was the first candidate gene that showed promise of an association with alcoholism. There is a growing body of scientific evidence that shows alcoholism has a genetic component. According to the American Academy of Child & Adolescent Psychiatry, children of alcoholics are four times more likely than other children to become alcoholics. Our understanding of the protein-coding function of the genome is still limited, and we have even less understanding of non-protein coding transcripts and genome elements regulating gene expression.
What gene is responsible for increased AUD risk?
The investigators also identified a subset of biological parents who had given up one child for adoption but had reared a second child themselves. If growing up in the environment of an alcoholic parent contributes significantly to alcoholism risk, this risk should be higher in the nonadopted sons and daughters of alcoholics, compared with the adopted-away sons and daughters. In addition to these findings, recent analyses demonstrate strong evidence for a locus that affects brain wave oscillations as measured by electroencephalography (Porjesz et al. 2002).
Approximately 75% of the families were ascertained via a proband in treatment for alcohol dependence. Initial recruitment prioritized families with at least three first degree relatives meeting criteria for alcohol dependence (i.e., densely affected) although many families include more than three individuals with AUD, hence the higher than population prevalence of alcohol dependence and AUD (Table 1). As shown in Figure 2, the proportion of families where more than half of the members met criteria for AUD ranged from 51% to 57%. Both probands and family members were characterized with age‐appropriate assessments, including a standardized diagnostic instrument designed by COGA, the Semi‐Structured Assessment for the Genetics of Alcoholism (SSAGA),10, 11 administered by trained interviewers.
