Genomics Essay

When one suggests that a behavior is determined genetically, then one horribly oversimplifies the situation, and negates the importance of culture and free will in determining how a person behaves.
One behavior that has gained large-scale acceptance as having a partial genetic cause is that of alcoholism. This genetic cause I expressed in terms of risk factor. It has often been noted that the children of alcoholics are more at risk of becoming addicted to alcohol than are other children.

in the last five or so years, technique arising from the Human Genome Project have made it possible to sequence human genes and actually try to pinpoint the locus of the genes associated with alcohol risk.

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One of the studies examined in this paper even goes so far as to suggest that the gene that is associated with alcoholism determines not only one’s risk for alcohol, but even the alcohol consumption habits of social drinkers.
This is significant because it suggests that even normal behavior is genetically determined. Some studies of alcohol addiction correlate the risk for addiction with social disorders in general, which can be seen from childhood. It is one of the points of this paper that such correlations do not represent a genetic predisposition to antisocial behavior, but rather a potential cause for alcoholism which is not necessarily genetic.

1) The first study examines beta-endorphin (An endorphin produced by the pituitary gland that is a potent pain suppressant) responses to alcohol among monozygotic (MZ, of or from one fertilized egg, as identical twins) and dizygotic (DZ, developing from two fertilized eggs, as fraternal twins) twins. The study was conducted at the University of Indiana, and the subjects were 51 MZ and 37 same sex DZ twins. The hypothesis was that beta-endorphin levels as a response to alcohol consumption are determined by genetic factors. Also, it is hypothesized in this study that a higher level of beta-endorphins in the blood as a response to consumption of ethanol is an indicator of heightened risk of alcoholism.

The study suggests that because beta-endorphins produce many of the feelings associated with alcohol intoxication (relaxation, euphoria, etc.), those who produce more beta-endorphins after consuming alcohol are at higher risk of becoming alcoholic.
2) The next study involved catechol-0methyltransferase (COMT), which is an enzyme involved in dopamine metabolism. Previous studies have shown that the gene for this protein is associated with alcoholism. The results of previous studies have suggested that enzyme is involved not only in alcoholism, but also social drinking. The results of the statistical analysis showed that in each of the three genotypes for COMT, there was no difference in distribution of age and other background. There were also no differences in frequency of alcoholism risk indicators between the different groups. Because none of the participants in the study were alcoholics or abstainers, all the subjects were assumed to be social drinkers. What the finding, then, suggests, is that COMT genotype is a significant factor in the patterns of social drinkers.

3) The third study deals with the populations of various Asian groups in which polymorphism in both the alcohol dehydrogenase-2 (ALDH2) and low Km aldehyde dehydrogenase (ALDH2) genes are prevalent. Certain variations of these genes result in the inability to properly process alcohol, causing a buildup of hemoglobin-associated acetaldehyde (HbAA). This causes discomfort and tissue damage, and has been hypothesized as an indicator of alcoholism in that those with the atypical gene tend not to consume much alcohol. This study confirms the findings of earlier studies that the atypical form of the ALDH2 does indeed result in the inability to fully process alcohol, and therefore results in the buildup of HbAA.

4) The fourth study also deals with the supposed lack of alcohol tolerance among some members of Asian communities. This study deals with the alcohol dehydrogenase genes (ADH2 and ADH3) that act on alcohol metabolism with different levels of efficiency. Those with certain genotypes process alcohol less efficiently and therefore experience discomfort upon alcohol consumption.
5) The fifth study , titled “Fetal Associative Learning Mediated through Maternal Alcohol Intoxication”, deals with the reactions of rats to alcohol administered prenatally.

The study consisted of administering alcohol along with an odoriferous substance to pregnant rats in order to see if the baby rat forms an association between alcohol and the odorous substance prenatally, which can be observed in the postnatal behavior. The result was that the rats that were administered alcohol and cineole (oil of wormwood) reacted differently to cineole that did the rats that were given just cineole, just alcohol, or nothing. This indicates that the rats formed an association between the two substances before birth. This observed association postnatally from prenatal stimuli indicates that prenatal learning based on alcohol is possible in rats.

6) The sixth study deals not specifically with genetics, but with behavioral dysfunction in childhood and adulthood, and its relationship to alcoholism. The study was conducted upon some 102 prisoners of a Japanese prison. The subjects were statistically examined based on their family history of alcoholism and antisocial personality disorder (ASP). Further comparisons of the information were used to determi8ne which characteristics were related to which. It was found that those prisoners which records of severe childhood conduct disorder had a much higher probability of becoming alcoholic and at an earlier time in life than those who didn’t have such a history. Subjects who had a history of childhood conduct disorder were also shown to be more likely to have been arrested for violence while intoxicated that those who had no childhood history, or whose family history included alcoholism but not ASP. This study suggests that behaviors surrounding alcohol consumption are influenced by factors other than simple familial risk. Behavioral disorders, whatever causes them, seem to have as much to do with the expression of alcohol dependence as does family history.

7) The seventh and final study examined deals with the association between parental history of alcoholism and behavioral problems in Native American children from Southern California. The study was conducted upon 96 children from various Southern California reservations.
The information for the study was gathered through a questionnaire that was filled out usually by the mother, which asked her to list the relatives who displayed significant alcohol related problems. This data was then analyzed along gender, age, and family history lines, to determine the various effects of family history of alcohol problems on the behavior of children.

The results of the analysis were different for boys and girls. Among boys it was found that familial history had no influence over the age at which behavioral problems were observed. However, males with alcoholic relatives did prove to be more prone to behavioral problems of both internal and external nature, without regards to age of expression.

The statistics on familial alcoholism as it relates to behavioral problems in children and adolescents is consistent with that for other ethnicities.

The first study claims in its introduction that genetic factors account for at least 40% of the risk of alcoholism. This kind of statistic should always be viewed with skepticism because there are too many variables. This study suggests that differences in risk of alcoholism are caused by the differences in beta-endorphin response. This claim is made because beta-endorphins produce many of the same effects attributed to alcohol. That is, they produce feelings of well being, relaxation and euphoria. The authors of the study hypothesize that because people genetically respond differently to alcohol consumption, those that produce more beta-endorphins are more likely to become addicted. There are a couple of problems with this study, however. The hypothesis is, after all, only a hypothesis. There was no background check done to see if those twins that responded with a greater than average beta-endorphin response were in fact at a higher risk of alcohol addiction based on family history. Another interesting aspect of this study is that DZ twins usually reacted differently from one another in te4rms of beta-endorphin response. This does indeed seem to illustrate that the reaction to alcohol is heritable, because MZ twins react the same. This demonstrates something further though. It suggests that DZ twins, which are similar but not identical in terms of genotype, respond quite differently. Parents and their children are even more genetically different that non-identical siblings, so it seems that a child would have a significantly different beta-endorphin response from its parent. The whole basis for the conclusion that risk for alcoholism is genetic is that DZ twins are not as similar in their response as are MZ twins. This demonstrates that parental alcoholism does not necessarily translate into similar risk of alcoholism in the child. A parent and child are not identical in their genome.

The second study suggests that the COMT gene, which is involved in dopamine metabolism, might be responsible for the drinking habits of not just alcoholics, but even social drinkers. One unique thing about this study is that it does not deal with a disorder or abnormality. It deals simply with whether the subject is homozygous for the low activity COMT, then dopamine is processed less quickly, which makes the high associated with alcohol consumption more distinct and longer.

The authors suggest that the observed differences in consumption could be caused by another gene or group of genes that are located near the COMT gene. The interactions of theses genes could cause higher alcohol consumption, and not simply low activity COMT genes.

The subjects of this study were not addicted to alcohol, and so, by definition, when and how much they decided to drink was a matter of personal choice. Therefore, if the study is to suggest that the COMT gene influences the choices and conscious thoughts that people have, we must be extremely cautious. A conscious decision, as the social drinker makes, is a very complex process that is difficult to attribute to genetics.

The fourth study which was the one that dealt with the alcohol dehydrogenase genes, deals with the findings of previous studies that the ADH3 gene and its varieties are associated with a deterrence to alcohol. This is because they are observed in higher frequencies among controls than alcoholics. The findings of this study are similar to those of previous studies in terms of data, but the interpretation is different due to differences in the statistical work, as well as more informed knowledge about the actual chromosomal location of the involved genes. The study suggests that all the ADH genes are located close to each other on one arm of chromosome 4, and so they are inherited in suite rather than individually. This shows that many studies oversimplify genetic causation. Previous studies had returned certain results because they failed to understand the way in which the genes they studied were inherited, and how they interact with other genes. This shows how lack of complete information and differences in statistical work can change the results of the study.

The next study differs in that it deals with rats instead of humans, but there is a very important point that can be made through its findings. The study administered alcohol and cineole to certain rats through their mothers to see if they would react differently after birth to the two substances than do the controls. The observation was that the rats that were given both alcohol and cineole did indeed form an association between the two, and that they reacted differently both to their mothers, cineole, and suckling than did the controls. This supports the hypothesis that rats can form associations based on substances, specifically alcohol, in a prenatal environment. These associations affect how the animals react to the chemicals, and to their mothers, after birth.

A point that can be taken from the findings of these studies is that a fetus may learn associations with alcohol that carry over into the postnatal world. The implications of this are large. If rats are capable of such learning, then humans probably are. The alcohol level in the mother was observed to be nearly the same as that in the fetus. This means that if a mother drinks during pregnancy, apart from the know dangers of this, the child can make associations based on the alcohol that will carry over into how the organism reacts to alcohol later in life.

The last two studies deal not specifically with genetics, but with childhood and parental behavioral problems that correlate with alcoholism.
The first of these deals with Japanese prisoners, a large percentage of whom are alcoholic Whatever the cause for behavioral problems, they seem to have influenced alcohol use, and reactions to it, more than risk factor. This study is important to an understanding of the genetics of alcoholism risk because it shows that alcoholism can be influenced, if not caused, by separate factor that is either learned or inherited from the parents.

The final study examined in this paper deals with severe conduct disorder among children of alcoholic Native-Americans. Most of the children of alcoholics (COAs) displayed behavioral disorders, whether internal or external.

This study is quite questionable, however. First of all, the sample size was quite small, with only 96 children used in the study. This means that the claim that only 7% of children had no alcoholic relatives works out to 6.72% kids. The results would have certainly been much different given a larger sample size. Furthermore, the way in which the subjects were found could have influenced the outcome of the study. Subjects were gathered on a voluntary basis based on response to fliers placed in various public locations. It does not seem very likely that people would have volunteered their time to go to the research center and fill out lengthy questionnaires unless there was some reward involved, such as a per-dium. It is quite possible that people exaggerated their reports of family alcoholism because they felt they were being paid for this information. It is also entirely possible that these people, mostly mothers, would have been reluctant to provide details about their own, and their family’s alcohol problems. Therefore the reports of alcoholism could also have been deflated substantially. This study illustrates how problems with the methods can have significant effects on the results.

The seven studies examined in this paper strongly suggest that there is some genetic component to risk for alcoholism. However, the situation is rarely so clear cut as having a specific gene that makes a person more at risk for alcoholism. Though the risk of alcoholism may have a genetic component, it is unclear how much of this is passed from parent to child. Twins might have the same genetic risk, but a child will not necessarily have the same risk as its parents or siblings. Genetics may code for a stronger high as the result of alcohol consumption that could lead to heightened drinking activity among social drinkers, but these people by definition have a choice, and this choice overrides the genetic component. Genetics can even cause people to react negatively to alcohol, and therefore lower the risk of alcoholism in those people with the “right” genes.
Overall, the situation is far more complex than this. Genes interact with one another. They may be inherited in suite, and dependent upon certain combinations for certain outcomes. The location of a gene may make it seem like it is important, when really it is that a gene is located near a different, involved gene that makes it seem relevant.

Also, as was shown in the study about rats, responses to alcohol can be learned. These responses can be learned even before birth, and may influence patterns of future use. This is important if we are examining familial risk. If a person drinks heavily because of prenatal conditioning due to maternal consumption, statistically it will look like the person inherited risk from the parent.

Alcoholism can also be influenced by other factors. Two of the studies correlated behavioral problems with alcohol use.

It is also true that the methods of study can influence results. Usually the information about alcohol consumption is gathered by questioning the subjects. This information is vital to statistical approaches. This information is also highly suspect.

From an anthropological perspective, alcoholism must have many contributing factors, of which genetics is just one. Human agency, learned behavior, and cultural influences must not be overlooked. Behavior, even given a large genetic component, is completely dependent upon environment. There has to be an environment to which to react. One might be an alcoholic in New York, and a Buddhist monk in Northern California, with the same genetics. An anthropologist must look at genetics as one wave in a sea of influences.



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