Genes can influence both alcohol consumption and dependence

Alcohol consumption and alcohol dependence are closely related, but the causes of susceptibility to the two may be different. New research has found that variation in long-term average alcohol intake is almost entirely due to genetic differences. Some genes affect both alcohol intake and dependence, while others affect only dependence.

Even though alcohol consumption and alcohol dependence are closely related, the causes of susceptibility to the two are not necessarily the same. A study in the August issue of Alcoholism: Clinical & Experimental Research looks at the genetic and environmental causes of variation in long-term alcohol consumption, and estimates what degree of overlap may exist with causes of susceptibility to alcohol dependence. Results indicate that variation in long-term average alcohol intake is almost entirely due to genetic differences, and that some genes affect both intake and dependence while others affect only dependence.

“Alcohol consumption is about how much a person drinks at some particular time, whereas alcohol dependence is more about the effects that alcohol has, or has had, on a person – their behaviour, their neurophysiology, and their relationships with other people,” explained John B. Whitfield, senior scientist at the Royal Prince Alfred Hospital in Sydney and first author of the study.

“Most people consume alcohol, at least in ’western’ societies, but only some consume it in large enough quantities which may do them harm,” said Whitfield, “similarly, only some are so affected by it that they meet the psychiatric criteria for ’alcohol dependence.’ The possible relationships between intake and dependence may be none, except during bouts of uncontrolled and extremely heavy drinking, or some overlap or common causes for each, or the same underlying causes for both. We sought to explore this relationship, which has received little attention in the past because most studies have concentrated on either one or the other.”

“We have known for some years that there are genetic influences on risk of alcohol dependence, but it has been challenging to separate out the extent of influence of a person’s genes from the influence of their childhood environment,” added Kate Conigrave, associate professor and staff specialist at Royal Prince Alfred Hospital in Sydney. “For example, if a person has an alcoholic parent, their childhood may be traumatic, and this may place them at increased risk of later alcohol dependence themselves. Up until now, most research on the genetics of drinking has focused on alcohol dependence rather than the genetics of alcohol consumption levels.

However, problems related to alcohol aren’t confined to dependent drinkers. Many alcohol-related problems like road trauma and high blood pressure occur in those who are drinking above recommended limits, but are still in control of their drinking.”

Researchers used data collected from three studies of Australian twins between 1980 and 1995. The 1980 study (n = 8,184) and the 1989 study (n = 6,570) examined items of alcohol consumption; the third study, begun in 1992 (n=5,996) and completed in 1995 with the acquisition of blood samples (n=3,378), examined items of alcohol consumption as well as possible diagnoses of alcohol dependence.

“In the people we studied, alcohol intake was reasonably constant across time – and this was expected – as a person who reports high intake at one time is likely to report high intake at other times,” said Whitfield. “However, we were able to show, by using twins as the subjects of our study, that variation between people in their long-term average intake is almost entirely due to genetic differences between people. Secondly, we found that higher reported alcohol intake, at any of the three times studied, was associated with a higher probability of alcohol dependence at some time in a person’s life. The association was mainly due to genetic effects on both alcohol intake and alcohol dependence, but our results also show that while some genes affect both intake and dependence, others affect only dependence.”

Whitfield noted that one of the strengths of this study is its examination of long-term averages of intake.

“Alcohol intake varies across time,” he said. “A person may drink quite a lot on a Saturday and much less on the following Monday, or quite a lot as a 20-year-old student and less as a 35-year-old accountant. Measuring alcohol intake on only one occasion will give a less reliable estimate of the long-term average than measurements on multiple occasions, and it is the long-term average which is important for both the harmful physical effects of alcohol and its association with decreased cardiovascular risk. The differences between people which do persist across time, or the differences in long-term average intake, appear to depend on genetic differences between them.”

’These findings do not mean individuals are predetermined to have an alcohol problem,” said Conigrave. “The situation is similar to that of coronary heart disease, where genes influence lipid levels and tendency to high blood pressure, and so increase risk of heart attack. Individuals can make decisions about their lifestyle which can improve their health and reduce their risk of harm. Similarly, individuals with a family history of heavy drinking or alcoholism can be aware that they may be at increased risk themselves, and can avoid situations that lead to heavy drinking, or can seek help early if problems emerge.”

Whitefield is hopeful that his research may help to change perceptions of alcoholism. “Naturally enough,” he said, “public attention focuses on the most extreme forms of alcohol dependence and literary and dramatic portrayals of ’alcoholics’ shape or reinforce this view. However, people with less extreme forms of alcohol dependence also report many alcohol-related problems, including relationship and employment difficulties, use of more alcohol than intended or in circumstances which make intoxication dangerous, and a need for larger amounts of alcohol to obtain the desired effects.”

“This study helps us bring prevention and treatment of alcohol problems into an increasingly rational domain,” added Conigrave. “Prevention and treatment efforts are often made difficult by society’s mixed views on alcohol: on one hand, a moralistic view that drinking problems are a sign of weakness or a deliberately chosen path; and on the other hand, society’s approval of episodic heavy drinking, particularly among young people or at any major celebration. From this study we can see more clearly that certain people are born with an increased risk of developing alcohol problems. An individual who is aware of a family history of alcohol-related problems needs to take efforts to reduce their own risk of problems, and society needs to provide support by reducing its tacit approval of heavy drinking and by providing alternative ways of celebrating that don’t centre on alcohol.”