Alcohol dependence has long been known to be more common among men than women. And now, Yale researchers think they have found the genetic root of this difference.

Researchers at the Yale School of Medicine analyzed the genetic code of 2,927 individuals and found that two mutations in a gene on the X-chromosome correlated with alcoholism in men but not women. The finding has implications for developing new treatments for alcoholism through targeting the gene and its protein products, said Yale professor of psychiatry and study author Lingjun Zuo.

“There is significant interest in studying sex differences related to addiction,” said study author and Yale professor of psychiatry and neurobiology John Krystal.

Sampling alcoholic subjects and controls from across seven states, the study revealed that mutations to the gene NLGN4X on the X-chromosome correlated with alcoholism. Since women have two copies of the X-chromosome, the only significant effects of the NLGN4X gene were seen in men — who only need one copy of the gene to be affected, Krystal said.

While the study did not investigate how the protein product of the gene caused alcoholism, previous research suggested the protein plays at least two key functions in the brain, said Xingguang Luo, associate research scientist for psychiatry at the Yale School of Medicine and study author. The protein works at the synapse of glutamate neurons, which are key in controlling excitation and inhibition in the brain. Luo said this suggests a deficiency in NLGN4X can lead to deficits in cognitive processing and an imbalance in impulsivity.

About 50 percent of variation in alcoholism is attributed to genetics while the other half can be influenced by environmental factors, said Yale professor of psychiatry Lingjun Zuo. The study revealed a correlation between the gene only among European-American males and not those of African descent, and Luo said this may be due to social factors having a greater impact on the drinking behavior of those of African descent.

The research team is continuing the study with a larger subject population. Zuo said he hopes to pursue how the gene could be targeted to prevent and treat alcoholism.

Almost 16,000 people die each year from alcohol-induced liver disease.