Cholinergic nicotinic receptor genes implicated in a nicotine dependence association study targeting 348 candidate genes with 3713 SNPs

摘要: Nicotine dependence is one of the world's leading causes preventable death. To discover genetic variants that influence risk for nicotine dependence, we targeted over 300 candidate genes and analyzed 3713 single nucleotide polymorphisms (SNPs) in 1050 cases 879 controls. The Fagerstrom test (FTND) was used to assess which were required have an FTND 4 or more. control criterion strict: subjects must smoked at least 100 cigarettes their lifetimes had 0 during heaviest period smoking. After correcting multiple testing by controlling false discovery rate, several cholinergic nicotinic receptor dominated top signals. strongest association from SNP representing CHRNB3, beta3 subunit gene (P = 9.4 x 10(-5)). Biologically, most compelling evidence a variant came non-synonymous alpha5 CHRNA5 6.4 10(-4)). This exhibited recessive mode inheritance, resulting individuals having 2-fold increase developing once exposed cigarette Other among signals KCNJ6 GABRA4. study represents powerful extensive studies date has found novel loci require confirmation replication studies.