the CHRNA5–CHRNA3–CHRNB4 nicotinic acetylcholine receptor subunit cluster and in the TTC12–ANKK1–DRD2 cluster, which includes DRD2, a dopamine receptor important in nicotine reward. In a community sample of 5000 Finns, the alleles most significantly associated with smoking were CHRNA5 Asp398Asn and an intronic variation within TTC12 (rs10502172). Adolescent carriers of three to four risk alleles at these two loci (20% of the population) had a threefold increase in odds of smoking regularly and 2.5-fold increased odds of occasionally smoking as compared to noncarriers, who constitute 9% of the population. Carriers of one or two risk alleles were at intermediate risk. A similar stepwise increase in risk with allele dosage was observed in adulthood, and again consistent with additivity (Fig. 5).
