Study Identifies New Gene Variation Associated with Increased Risk of Nicotine Addiction

Europeans and European/African Americans with a variant of the DNA Methyltransferase 3 Beta (DNMT3B) gene have an increased risk of developing nicotine dependence, smoking heavily, and developing lung cancer, a new study published in the journal Molecular Psychiatry shows.

According to Hancock et al, the new genetic variant highlights the importance of genetically influenced regulation in brain on the risks of nicotine dependence, heavy smoking and consequent lung cancer. Image credit: Martin Buedenbender.

According to the World Health Organization, the tobacco epidemic is one of the biggest public health threats the world has ever faced, killing more than 7 million people a year.

More than 6 million of those deaths are the result of direct tobacco use while around 890,000 are the result of non-smokers being exposed to second-hand smoke.

Nicotine dependence, which reduces the likelihood of quitting smoking, is a heritable trait with firmly established associations with several genetic variants.

To search for additional genes that influence nicotine dependence, Dr. Dana Hancock of RTI International and co-authors conducted a genome-wide association study (GWAS) meta-analysis of nicotine dependence, totaling 38,602 smokers — 28,677 Europeans/European Americans and 9,925 African Americans.

“In this largest-ever GWAS meta-analysis for nicotine dependence and the largest-ever cross-ancestry GWAS meta-analysis for any smoking phenotype, we reconfirmed the well-known CHRNA5-CHRNA3-CHRNB4 genes and further yielded a novel association in the DNMT3B gene,” the researchers said.

The genetic variant was linked to an increased risk of nicotine dependence by testing nearly 18 million variants across the genome for association with nicotine dependence.

The variant was also tested in independent studies and found to associate with heavier smoking and with increased risk of lung cancer.

“This new finding widens the scope of how genetic factors are known to influence nicotine dependence,” Dr. Hancock said.

“The variant that we identified is common, occurring in 44% of Europeans or European Americans and 77% of African Americans, and it exerts important effects on gene regulation in human brain, specifically in the cerebellum, which has long been overlooked in the study of addiction.”

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D.B. Hancock et al. Genome-wide association study across European and African American ancestries identifies a SNP in DNMT3B contributing to nicotine dependence. Molecular Psychiatry, published online October 3, 2017; doi: 10.1038/mp.2017.193