Genes play important role in risk for dependence on illicit and licit drugs

The genes that play a role in illegal drug abuse are not entirely the same as those involved in dependence on legal substances like alcohol and nicotine, and caffeine addiction appears to be genetically independent of all the others, according to a study led by Virginia Commonwealth University researchers.

The findings may guide efforts by researchers to use molecular genetic tools to localize genes that influence risk for psychoactive drug abuse or dependence, or A/D.

In the November issue of the Archives of General Psychiatry, a journal of the American Medical Association, researchers examined the degree to which genetic and environmental risk factors for dependence were shared between illicit and the more commonly used licit psychoactive drugs among men and women.

“We wanted to know whether there was a single set of genes that influence risk for A/D on all substances,” said Kenneth S. Kendler, M.D., a professor of psychiatry and human genetics in VCU's School of Medicine and lead author on the study.

“Our findings suggested two genetic factors - one which strongly impacted on risk for A/D of illicit drugs, such as cannabis and cocaine, and one that impacted on risk for A/D of licit drugs, including caffeine, nicotine and alcohol. However, these two factors were rather strongly correlated,” he said. “It was also of interest to note that the genes for caffeine A/D were pretty independent of those found for all the other substances.”

Kendler and his colleagues examined lifetime symptoms of abuse of and dependence on marijuana, cocaine, alcohol, caffeine and nicotine among 4,865 male-male and female-female twin pairs through a series of personal interviews. The data collected from the interviews was analyzed using the methods of structural equation modeling.

The twin pairs that participated were from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders. These twin pairs were ascertained from the Virginia Twin Registry. The Virginia Twin Registry, now part of the VCU Mid-Atlantic Twin Registry, contains a population-based record of twins from Virginia, North Carolina and South Carolina.

“This study also confirmed the strong role that genetic factors play in influencing our vulnerability to drug abuse and dependence,” Kendler said. Heritability – the proportion of individual differences in risk due to genetic differences – was estimated in this study to be more than 70 percent for cocaine, cannabis and nicotine A/D, nearly 60 percent for alcohol A/D, and, interestingly, quite a bit lower – around 35 percent – for caffeine A/D, he said.

In previous studies, researchers examined an array of illegal substances and did not include commonly used licit drugs, and included only male participates. This was the first study of its kind to examine across the sexes and degree to which risk factors for dependence were shared between illicit and licit drugs.