Penn study finds genetic differences between heavy drinkers and alcoholics

A huge analysis of drinking patterns among veterans has found genetic distinctions between heavy drinkers and alcoholics, according to a study published last week in the journal Nature Communications.

The research team, co-led by the University of Pennsylvania and Yale University, found that the two groups shared some genetic variants but not others. This has implications for the development of medications to treat harmful drinking and for identifying who is most at risk.

The study analyzed data from 275,000 people in the Million Veteran Program, sponsored by the Department of Veterans Affairs. The vast majority were male, but the subjects were racially diverse. The researchers looked for genes associated with the level of drinking and with alcohol use disorder (AUD), an uncontrolled form of drinking, often called alcoholism, that affects about 15 million Americans. Alcoholics who are not in recovery are heavy drinkers, but not all heavy drinkers are alcoholics. For example, 39 percent of the Caucasian heavy drinkers in the study were not classified as alcoholics.

The results are “evidence of something I think many people have thought or wondered about, that is, is heavy drinking the same thing as alcohol use disorder, and what we found is that it both is and it isn’t,” said Henry Kranzler, a psychiatrist who is director of Penn’s Center for Studies of Addiction. “It’s overlapping, but it’s not the same thing.”

The study found 18 genetic variants that were associated with alcoholism or the amount that people drank. Five of the variants were related to both alcohol consumption and addiction. Eight were associated only with level of drinking and five with AUD only. Some of the gene variants were protective against heavy drinking or AUD, Kranzler said. While some of the gene variants had previously been identified, researchers do not know what role most of them play in the body.

Previous studies have found that 50 percent to 60 percent of the risk for developing AUD is heritable, Kranzler said.

Researchers typically define heavy drinking as five or more drinks a day for men and four or more for women. Drinking is considered hazardous or unhealthy when it exceeds seven drinks in a week for women and 14 for men. The results of studies on whether some level of drinking is beneficial have been varied and controversial.

AUD is defined by an inability to control drinking despite negative social or medical consequences. Alcoholism tends to be more socially destructive, but heavy drinking is still bad for the liver and other organs, including the brain, Kranzler said. He said that most heavy drinkers as well as most alcoholics are not physically dependent on alcohol. The most common onset of AUD is the late teens, although the diagnosis often comes later.

Twenty percent of people in the study were diagnosed with AUD.

The study also looked for other types of genetic correlations with alcohol consumption and alcoholism. The researchers found that the genetic profile variants associated with higher alcohol consumption were genetically tied to lower weight and less heart disease and diabetes. AUD was genetically correlated with lower intelligence and education as well as smoking, insomnia and psychiatric problems.

The researchers also found evidence that those with the gene variants associated with heavy alcohol use or AUD had more actual medical problems — not just genetic risk for them. The gene variants associated with higher alcohol consumption correlated with increased risk for alcoholic liver damage. The genetic profile for AUD was associated with smoking and multiple psychiatric disorders.

Kranzler said different strategies may work to reduce drinking among heavy drinkers or alcoholics. Advice may be enough for heavy drinkers. "They may be better able to reduce their drinking, and they may not need a pharmacological treatment to do it," he said.

For alcoholics, though, the impaired ability to control their behavior makes it harder to stop on their own. “You can’t simply will your way out of that situation,” he said.