Association of a polymorphism in the NRXN3 gene with the degree of smoking in schizophrenia: A preliminary study

Whole genome scan studies have recently identified the NRXN1 and NRXN3 genes as potential contributing factors in the risk for nicotine addiction. We have genotyped 15 single nucleotide polymorphisms (SNPs) spanning the NRXN1 and NRXN3 genes in 195 unrelated patients with schizophrenia for whom information about their smoking status and number of cigarettes smoked per day (CPD) was obtained. The NRXN3 marker rs1004212 was significantly associated with quantity of tobacco smoked. Individuals homozygous for the C allele of rs1004212 smoked more cigarettes per day than heterozygous individuals. We found no significant association of markers within the NRXN1 gene with the risk of smoking or the quantity of tobacco smoked. Because of the relatively small sample size, this is a preliminary study. However, this candidate gene study supports the observations of molecular studies implicating the NRXN genes in drug addiction and suggests that variants in the NRXN3 gene could contribute to the degree of nicotine dependence in patients with schizophrenia.