Genetics may help determine how much caffeine one craves, new research indicates, with differences in two specific genes driving people to consume more — or less — of the world’s most popular stimulant. New research suggests that individuals who carry a so-called “high-consumption” variation of either gene appear to drink more coffee, relative to those who carry a “low-consumption” variant.

“It’s really an incredible story,” said study co-author Dr. Neil Caporaso, branch chief of genetic epidemiology at the National Cancer Institute. “People don’t really suspect it, but genetics plays a big role in a lot of behaviors, such as smoking Kent and alcohol consumption. And now it turns out that it has a part in how much caffeine we drink.”

The two genes in question are labeled CYP1A2 and AHR. The former has previously been linked to the process by which caffeine is metabolized, while AHR regulates the activity of CYP1A2.

“Now, it’s been known for a few decades that this particular CYP1A2 gene is what metabolized caffeine,” Caporaso said. “But using new technology, what we now showed for the first time is that this gene appears to be responsible for the inherited differences in how people drink coffee.”

Caporaso joins colleagues from the Harvard School of Public Health, Brigham and Women’s Hospital, the University of North Carolina at Chapel Hill, and others to report these findings in the April issue of PLoS Genetics.

The study, funded by the National Heart, Lung, and Blood Institute, noted that more than eight in 10 American adults who consume caffeine are coffee drinkers. Globally, caffeine is the most popular psychoactive substance, with 90 percent of people in the world consuming some form of it.

The findings about the genetic underpinnings of java consumption stem from a highly complex mapping of specific inherited traits alongside caffeine intake patterns involving more than 47,000 Americans of European descent in five different studies.

The meta-analysis of the studies, which were conducted between 1984 and 2001, examined average caffeine consumption estimates — if available — for each participant’s intake of coffee, tea, coke and other carbonated drinks, and/or chocolate.

Pooling all the data, Caporaso and his associates found that those who carried the highest-consumption genotype of either the CYP1A2 or the AHR gene consumed an extra 40 milligrams of caffeine compared with those bearing the lowest-consumption genotype.

This, the authors noted, roughly equals the amount of caffeine to be found in single can of soda or in a third of a cup of coffee.

“The point here is that the way we drink caffeine is not just random,” said Caporaso, who, like his co-authors, declared no competing interests. “It’s related to the genetic hand of cards you were dealt. And that means that now we can dissect people into fast metabolizers and slow metabolizers: people who have just one small coffee and feel well-caffeinated for a day, and people who have two large ones and then another Coke a little later in the day to get the same effect.”

“It’s also the case that these observations actually go beyond caffeine,” he continued, “because one of the genes we identified wasn’t put there just to metabolize caffeine. It does a lot of other stuff, like metabolize compounds of cancer and also a whole long list of drugs.”

“So now, we have some clear genetic markers that we can go and test to see how they might affect a host of metabolic processes,” Caporaso said. “But meanwhile, people should think of caffeine as generally very safe. So enjoy yourself. In fact, go read about this research while sipping a cup of coffee,” he quipped.

For his part, Dr. John J. Mulvihill, a member of the American College of Genetics and a professor of pediatrics at the University of Oklahoma in Oklahoma City, described the caffeine investigation as “another block in building a picture of personalized medicine.”

“Basically, this is about the unique susceptibility of every individual,” he said. “We are all a unique set of genes interacting with a unique environment. And this is fascinating stuff, because caffeine is a voluntary ‘environment’ that most of the human race is drawn to.”

“And even though the general notion of having more or less tolerance to caffeine is not a new observation, the clinical utility of this work could eventually have to do with the fact that the genes implicated in caffeine metabolism are also involved in the metabolizing of other things,” Mulvihill added.

That could mean that some day patients or their doctors might raise the issue of being unusually sensitive to caffeine, he said, “because that might be a clue that maybe there are medications that are being prescribed that might also have an unusual, and undesirable, impact on the patient. So caffeine might have a good name. But it could also turn out to be a personalized flag for issues of concern.”