Genes Contributing to the Development of Alcoholism: An Overview Alcohol Research: Current Reviews
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. In recent years there have been attempts at empirical classification of alcoholics into clinically relevant and potentially genetically distinct subgroups based on the large National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) 2 that will be discussed later. Finally, the diagnostic criteria for the alcoholism phenotype (now called alcohol use disorder (AUD)) have just been radically revised in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) 3. The aim of this review is to highlight some recent studies in human research that are of particular interest and not to provide exhaustive coverage of the literature. Like many other complex traits, alcoholism appears to be clinically and etiologicaly hetrogenous13. This implies that there might be several steps and intermediate conditions in the development of AUD.
Alcohol metabolism and the risk for AUD
Kaij conducted followup interviews with alcoholic twins and their co-twins,3 showing that twins having at least one Temperance Board registration exhibited a fivefold increase in probability of being diagnosed as alcoholic, thereby confirming the validity of registrations as a measure of alcohol problems. He also noted, however, that those twins with social problems were likely to be overrepresented among Temperance Board registrants. Further, most clinical trials and behavioral studies have focused on individual substances, rather than addiction more broadly. According to a review from 2016, genes that promote alcohol metabolism and the production of enzymes, such as alcohol dehydrogenase and aldehyde dehydrogenase, can be protective against AUD. Your genetics can influence how likely you are to develop AUD, but there’s currently no evidence of a specific gene that directly causes AUD once you start drinking.
COGA Collaborators
Levy and Kunitz (1971) attributed the variability between tribes to differences in their tolerance of deviant behavior, which in turn lead to different levels of acceptable drinking. Other analysts have attributed the various rates to different socioeconomic conditions of reservations (Liban and Smart 1982; Silk-Walker et al. 1988; Austin et al. 1993). May (1996) reviewed the eight available studies on the prevalence of drinking among American Indian adults and found variation in the proportion of “current drinkers”1 from a low of 30 percent to a high of 84 percent; the rate among the general non-Indian population was 67 percent (May 1996).
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Alcohol levels in common drinks rangefrom approximately 5% (1.1 M) for beer, 11-15% for wine (∼3M) and 40% for spirits (∼9 M). The oral cavity and esophagus aredirectly exposed to those levels, and the liver is exposed to high levels from theportal circulation. Thus it is not surprising that diseases of the GI system,including cirrhosis, pancreatitis, and cancers of the upper GI tract are affected byalcohol consumption80-86. Genetic disorders are diagnosable conditions directly caused by genetic mutations that are inherited or occur later in life from environmental exposure. Your genetic risk refers to the likelihood that specific genes or genetic variants passed down to you will lead to a particular condition.
- Thus, prevalence rates for alcoholism are available for the total sample of biological parents and adoptees.
- In many cases, the initial linkage studies were followed by moredetailed genetic analyses employing single nucleotide polymorphisms (SNPs) that weregenotyped at high density across the linked regions.
- Alcohol tolerance means that equal amounts of alcohol lead to lesser effects over time, generating a need for higher quantities of alcohol to feel the same desired effects.2 While it may seem like there is a genetic predisposition for alcohol tolerance, tolerance is not inherited.
- Currently, many different agencies implement alcohol policies and claim some responsibility for lowering the rates of alcohol use.
- Clearly very large sample sizes are required to detect large panels of rare variants and there are significant bioinformatic requirements to deal with vast quantities of data.
- It has also been suggested that some of the energy ingested as alcohol is ‘wasted’, due to the activation of the inefficient hepatic microsomal ethanol-oxidizing system (MEOS).
Genes Contributing to the Development of Alcoholism: An Overview
This study, however, did not control for PA levels and only assessed alcohol intake on a yes/no scale 42. Based on the fact that 1 gram of alcohol provides 7.1 kcal (29 kJ) and studies showing that energy consumed as alcohol is additive to that from other dietary sources 5, increased energy intake with alcohol use can certainly promote a positive energy balance and ultimately weight gain. However, a clear cause-and-effect association between alcohol intake and weight gain is not apparent based on the mixed and conflicting available evidence on the topic. Given that both excessive alcohol intake and obesity are of public health concern, a better understanding of the association between alcohol consumption and excess body weight is warranted. Although variations in individual ADH and ALDH genes can affect risk for alcoholism, it is important to remember that no one gene determines this risk. An increasing number of genes not related to ethanol metabolism also affect risk (Edenberg and Foroud 2006).
- Other enzymes, such as cytochrome P450 (e.g., CYP2E1), metabolize a small fraction of the ingested ethanol.
- AUD isn’t directly caused by genetics, but genetics may predispose you to developing AUD later in life.
- Many tribes attempted to restrict commerce in alcohol and were successful for short periods of time (Smart and Ogborne 1996).
- These findings reinforce the notion that there are different paths to alcohol dependence and different physiological pathways underlying them.
In lieu of such a consensus, it would be impossible for any one responsible community faction to “enforce” a common standard. Cultural beliefs among many Indian tribes place responsibility for behavior outside the person what percentage of alcoholism is genetic and in the realm of spiritual forces, both good and evil. According to these beliefs, the resolution to a particular problem lies in the ceremonial realm, in which a person remains relatively passive while rituals are performed to resolve the imbalance of powers.
- The scientific and academic communities must therefore help guide this process by distinguishing true physiological relations from false claims and by encouraging socially responsible uses for these discoveries.
- Many researchers (Mail and McDonald 1980; May 1996) have reported a style of drinking frequently engaged in by both Indian youth and adults in which drinkers consume large amounts of alcohol in a short period of time and continue drinking until the supply is gone.
- As might be expected, people with this slow-metabolizing gene variant also have a decreased risk, by up to sixfold, for alcoholism, so it is an example of a genetic variation that can protect against developing the disorder.
- Based on similarities in their amino acid sequences and kinetic properties (e.g., the rate at which ethanol is oxidized), the seven ADH types have been divided into five classes (see Table 1).
- Our research group recently discovered, for example, that variation in a gene encoding a receptor involved in taste perception, known as hTAS2R16, is significantly linked to alcoholism in the COGA subjects.
- Genome-wide data on 14,904 DSM-IV diagnosed AD individuals and 37,944 controls from 28 case/control and family-based studies were meta-analyzed for PGC’s AD GWAS.
However, one cannot conclude from this finding that rearing environment in general has little impact on alcoholism risk. In less than 5 percent of adoptive families did either parent have a Temperance Board registration, implying that adoptees were being placed in low-risk environments. A separate adoption study conducted in Scandinavia (Bohman et al. 1981; Cloninger et al. 1981, 1985) replicated the Copenhagen study findings using different procedures. Although additional information was available from other agencies (e.g., welfare reports and national health insurance records) and was used in some articles by Cloninger and colleagues, the data reanalyzed here are limited to Temperance Board registration data as reported by Cloninger and colleagues (1985). There is evidence that heavy episodic (binge) drinking, which results inexposure of tissues to high levels of alcohol, is particularly harmful81, 87, 88. Binge drinkingis generally defined as a man consuming 5 standard drinks within 2 hours; women are typically smaller and have a lower percentage of body water, so 4 standarddrinks can reach similar alcohol levels.