The Genetics of Alcoholism

Building off of work done last year, a team of researchers led by scientists at the University of California, San Diego School of Medicine has identified new genetic variants associated with alcohol dependence in what is the largest genetic study of alcoholism ever done.

The study, published in the American Journal of Psychiatry, found more than a dozen genetic variants associated with alcohol abuse or “alcohol use disorder,” and they found an overlapping association between alcohol abuse and psychiatric conditions such depression, attention-deficit disorder, and schizophrenia. There was also overlap with other substance abuse issues including smoking, cannabis use and “increased consumption of multiple drug types.”

 

“We have shown that genetic risk for problematic alcohol drinking overlaps with psychopathology, including increased genetic risk for major depression, schizophrenia, and attention-deficit/hyperactivity disorder,” said co-author of the study Sandra Sanchez Roige, Ph.D., at , of UC San Diego School of Medicine’s Department of Psychiatry.

 

The researchers used a questionnaire completed by participants to differentiate problem drinking from causal alcohol consumption, an important distinction in this study. Researchers were able create a score for alcohol use, relying on an Alcohol Use Disorder Identification Test (AUDIT) that measures a broad spectrum of alcohol consumption. This in turn allowed the researchers to distinguish between casual drinking, alcohol abuse, and alcohol addiction, and identify that high scores were genetically correlated with a clinical diagnosis of alcohol dependence. The study also found that in contrast occasional drinking is associated with lower rates of depression, longer time in school and lower rates of obesity.

 

“In fact, using this questionnaire in a population not ascertained for alcohol use disorders we have been able to achieve the largest sample size even obtained in the field of alcohol use disorders,” said Sanchez Roige.

These findings are important for researchers because of similar overlap with other addictive behavior, said lead researcher Prof. Abraham Palmer.

Prof. Abraham Palmer

 

“In terms of sample size, this is the largest sample ever used for a genetic study of alcoholism,” Palmer said. “Unlike prior efforts that focused on clinical diagnoses, which are relatively slow expensive on a per subject basis, our study used a 10-item screening questionnaire, that was originally developed by the World Health Organization. As a result, our collaboration with 23andme was done entirely via the Internet. That means it scales well; indeed, we plan to increase the sample size dramatically in the coming years.”

 

The study is also important because of the massive health and socio-economic impacts from substance abuse in general. Even just looking at alcohol alone there is a vast health cost, with more than 3.3 million people worldwide die each year from excessive alcohol use, according to the World Health Organization. In the United States the economic costs of alcohol abuse are estimated to be as high as $249 billion each year, according to the Centers for Disease Control.

While there are environmental and social factors that influence the risk for alcoholism, there is also a genetic component.

Scientists have learned through studies of identical and non-identical twins that alcohol use disorder is heritable, with genetic factors accounting for about half of the risk of alcohol dependence. But finding the genes that influence alcoholism has been challenging. Part of the challenge has been to gather a study that is large enough to detect a genetic signal, said Palmer.

 

But the ability to tap into “big data” such as 23andMe’s research cohort as well as the UK Biobank, which Palmer and his team used for this study, has opened up new research opportunities for those studying behavioral traits — like addiction and substance abuse — as well as neuropsychiatric conditions and personality.

 

With data from more than 140,000 individuals, including aggregated data from 20,000 23andMe customers who consented to participate in research, this study was large enough to detect more than a dozen genetic variants associated with the alcohol use disorder.

 

The study identified more than a dozen variants associated with alcohol use disorder, many of them identified for the first time. The top hits were near genes that play a role in alcohol metabolism. While there is overlap between alcohol use disorder and alcohol consumption, the researchers did further analysis and found “distinct genetic architecture” differentiating alcohol abuse versus alcohol consumption. And these distinctions will be important for identifying the genetics of addiction, the researchers said.

 

“By studying different subsets,” the researcher said. “We identify genetic factors that may be specific to problem drinking.”

 

The researchers believe that even larger studies may help to differentiate the genetics behind alcohol addiction.

 

“Our main focus is on further increasing sample size,” said Palmer. “Also, the present study focused on individuals of European ancestry, that’s because we had the largest sample in that group, however, we are very much interested in developing well powered samples in other l populations.”

 

Beyond that, Palmer and his team want to develop better understand how the genes they’ve identified might influence these traits, but using animal and cellular models.

 

“Those biological insights are critical to potentially developing  better strategies for prevention and treatment of alcoholism and related psychiatric disorders,” he said.