DNA samples from about 6,000 people were analyzed for about 500,000 known variations in the human genome to determine whether any of the variations predicted cigarettes per day during the period of heaviest smoking for the subjects.

A second population of about 8,000 people, whose smoking histories were known, was analyzed in a similar manner, the result again suggesting that variations in these two genes increased risk for heavy smoking. Taken together, the two studies provide evidence that variations in the alpha 3 and alpha 5 nicotinic receptor subunit genes play a significant role in risk for nicotine addiction.

The researchers said the alpha 3 and alpha 5 nicotinic receptor subunits will be made targets for new smoking cessation medication development programs by pharmaceutical companies.

The findings by researchers from the University of Pennsylvania School of Medicine, GlaxoSmithKline and the University of Toronto are published online in advance of publication in Molecular Psychiatry.