Table 4.

Functional studies of variations associated with smoking in the 47 ND susceptibility loci

Chr.	Gene	Experiment	Variation [Effect Allele]	Effect	Ref.
1	CHRNB2	In vitro gene expression assay	rs2072658 [A]	Reduced expression	167
6	OPRM1	PET brain imaging	rs1799971 [G]	Binding potential & receptor availability change	67, 168, 169
8	CHRNA2	Electrophysiology assay	rs141072985 rs56344740 rs2472553	nAChR function change	170, 171
	CHRNB3	In vitro gene expression assay	rs6474413 [C]	Reduced expression	172
		ChIP and in vitro gene expression assay	rs4950 [G]	Eliminated TF binding and reduced promoter activity	129
9	DNM1	In vitro gene expression assay	rs3003609 [T]	Reduced expression	113
11	BDNF	fMRI, 1H-MRSI, and immunoenzyme assays	rs6265	Different brain activation, BDNF secretion, and subcellular distribution	143
	DRD4	fMRI	exon 3 VNTR	Different brain activation	173
15	CHRNA5/A3/B4	Imaging Series of in vitro assays Electrophysiology and FLEX station	rs16969968 [A]	Brain circuit strength prediction Altered response to nicotine agonist Lower Ca permeability and increased short-term desensitization	7, 174, 175
17	SLC6A4	In vitro gene expression assay In situ hybridization SPECT imaging	5-HTTLPR	Transcriptional efficiency and expression change	176-178
19	CYP2A6/B6	Please refer to Tricker179 for a comprehensive summary
20	CHRNA4	Electrophysiology assay	exon 5 haplotype	Different receptor sensitivity	180
22	COMT	Enzyme activity assay	rs4680 [A]	Less enzyme activity	181

Abbreviations: ChIP, chromatin immunoprecipitation; fMRI, functional magnetic resonance imaging; ¹H-MRSI, ¹H magnetic resonance spectroscopic imaging; nAChR, nicotinic acetylcholine receptor; PET, positron emission tomography; SPECT, single-photon emission computed tomography.