A study in the April 2005 issue of Alcoholism: Clinical & Experimental Research looks at what impact interactions between a polymorphism of the serotonin transporter (5-HTT) gene and family relations may have on adolescent drinking.
"Hereditary factors can explain quite a lot of the variance in alcohol consumption," said Kent W. Nilsson, a researcher at the Centre for Clinical Research at Uppsala University in Sweden and corresponding author for the study. "Likewise, environmental factors can have a fairly high impact on alcohol consumption. In addition, other studies have shown that hereditary risks may be amplified in an unfavourable environment, and that different, and sometimes contradicting, results of gene associations may be explained by different environmental/background factors of the study participants."
"Most complex behavioral disorders such as alcoholism have a heritability in the range of 40 to 60 percent, so we know there must be an important influence of life experience as well, and potential for interactions," said Markus Heilig, clinical director of the National Institute on Alcohol Abuse and Alcoholism. "The problem is that these disorders are also polygenic. That means that each specific locus is only likely to contribute a small component of disease risk, a few percent at best. That in itself is hard enough to find unless studies are very large. Finding the interaction of course is even more challenging."
Nilsson said that he and his colleagues chose to examine the 5-HTT gene because of its relationship with many alcohol-correlated factors such as personality, anxiety, and depression.
"Within my field of sociology," he said, "a long tradition of research has shown a connection between high alcohol consumption and poor inter-individual relations, especially close or intimate relations. Therefore, it seemed likely that adolescents with a hereditary risk should have an additional risk if they also have poor relations with their parents."
Predicting Adolescent DrinkingThe researchers interviewed 200 (81 males, 119 females) 16- and 19-year-old Swedish students about their alcohol experiences as well as the quality of relations within their families. Each of the interviewed students also gave blood samples to be genotyped for polymorphisms of the 5-HTT gene.
Results indicate that both a functional polymorphism of the 5-HTT genotype and family relations, as well as interactions between these two variables, can predict adolescent alcohol consumption. Specifically, adolescents with the LS (long/short) variant of the 5-HTT gene and with family relations rated as "neutral" or "bad" had a 12- to 14-fold increased risk for high-intoxication frequency. Conversely, results suggest that a favorable family milieu can protect against a genetic vulnerability.
Hereditary Risk Can Be Prevented"Study results help us see an interaction of the gene and the environment," said Nilsson, "and that a hereditary risk for alcohol consumption 'amplifies' the risk from a poor environment and/or vice versa. Furthermore, our results suggest that a hereditary risk may be prevented if the environment is good."
"The approach of looking at extremes of normal behavior in relation to genetic variants is probably one that should be pursued more," said Heilig. "The importance of looking at antecedents of alcohol-use disorders cannot be overstated. In addition, the role of the family environment should be explored, since we have so far very little knowledge of 'shared environmental factors' behind alcoholism, as opposed to 'non-shared environmental factors', such as a serious disease. However, there is a caveat here since kids get both their genes and their family environment from their parents, the potential for confound is enormous, and disentangling the influence of the respective factors very challenging." He suggested additional research with larger numbers of participants.
Multiplying the RisksHeilig also cautioned against overestimating the role of molecular genetics in "identifying" individuals at risk and targeting them for prevention. "The total amount of variance in risk for high drinking explained here is 11 percent," he said. "On the other hand, we know that if you are a boy and your father was an alcoholic, those factors alone multiply your risk almost nine-fold. If in addition you tolerate unusually high amounts of alcohol when you start drinking, your risk is even higher."
Heilig acknowledged that identification of gene variants that confer risk may be "intellectually rewarding," but he suggested that readers pay just as much attention to "risky behaviors" that become apparent early in life.