Nicotine Dependence Gene Mapped to Chromosome 5

Genes that appear to increase the risk of nicotine dependence are likely to be found on several locations, including a region of chromosome 5, according to a Yale School of Medicine study in Biological Psychiatry. “These data add to the growing evidence for specific locations for genes that influence risk for nicotine dependence,” said Joel Gelernter, professor of psychiatry, genetics and neurobiology and lead author of the study. “The chromosome 5 linkage signal is our most remarkable result statistically.”

Genes that appear to increase the risk of nicotine dependence are likely to be found on several locations, including a region of chromosome 5, according to a Yale School of Medicine study in Biological Psychiatry.

“These data add to the growing evidence for specific locations for genes that influence risk for nicotine dependence,” said Joel Gelernter, professor of psychiatry, genetics and neurobiology and lead author of the study. “The chromosome 5 linkage signal is our most remarkable result statistically.”

He said the finding is significant since any ability to predict nicotine dependence based on genes that influence risk could be useful and might help reduce the number of persons who begin smoking. The World Health Organization estimates that more than one billion people smoke, and the number is continuing to increase.

“Nicotine dependence, like alcohol, cocaine, and opioid dependence, is heritable,” Gelernter said. “It has been estimated that 60 percent or more of tobacco use is associated with heritable factors. We are using genetic linkage analysis can be used to identify genomic risk loci.”

The study population included 634 small nuclear families with multiple individuals affected by cocaine or opioid dependence. Most also provided nicotine dependence information. Study subjects came from two ethnic backgrounds — European-Americans and African-Americans.

The results showed there were a number of loci that appeared to contribute to risk and distinct differences between the two groups. The researchers also found one significant genome-wide linkage on chromosome 5 for the African-Americans and a strong linkage on chromosome 7 for European Americans.

“The overall pattern of results supports the interpretation that at least some genetic determinants of nicotine dependence overlap between different, differently ascertained populations,” Gelernter said, comparing his results to previously published observations. “The chromosome 5 finding in African-Americans might be more specific to this sample, either because of the population or because of the way the sample was ascertained.”

Co-authors include Michael Krauthammer, M.D., and James Poling of Yale; Henry Kranzler, M.D., the University of Connecticut Medical School; Roger Weiss, M.D., Harvard; Carolien Panhuysen and Lindsay Farrer, Boston University, and Kathleen Brady, M.D., Medical University of South Carolina.

The work was supported by the National Institutes of Health and the U.S. Department of Veterans Affairs.

Biological Psychiatry 61: 119-126 (January 1, 2007)

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