For NIC, a field-wide meta-analysis is also needed. For smoking behavior, large meta-analyses have been conducted. 92,102,103 The strongest finding is an association of smoking quantity with a cluster of nicotinic receptor genes (CHRNA5-CHRNA3-CHRNB4) with an effect size corresponding to one cigarette per day, and there may be several independent associations. 104 Associations to this region have also bee reported for lung cancer. 105,106 A recent study showed that Chrna5 null mice had higher nicotine intake due to loss of an inhibitory effect on brain reward systems. 107
