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Table

- Molecular genetics of nicotine dependence and abstinence: whole genome association using 520,000 SNPs

Table 1

Nicotine dependent vs control comparisons

*Gene/Cluster*	*Class*	*Chr*	Bp	*Rep Pos Snps*	*monte carlo p*	*Description*

CNTN6	CAM	3	1,280,415	11	0.00059	contactin 6
LRRN1	CAM	3	3,769,591	20	0.00007	leucine rich repeat neuronal 1
SEMA3C	CAM	7	80,111,952	9	0.00120	sema domain, immunoglobulin domain (Ig), short basic domain, secreted, (semaphorin) 3C
CSMD1a	CAM	8	3,184,850	11	0.00083	CUB and Sushi multiple domains 1
CSMD1b	CAM	8	3,653,990	13	0.00095	CUB and Sushi multiple domains 1
PTPRD	CAM	9	8,310,837	13	0.00047	protein tyrosine phosphatase, receptor type, D
LRRN6C$	CAM	9	29,153,017	6	0.00118	leucine rich repeat neuronal 6C
CDH13	CAM	16	81,647,004	11	0.00198	cadherin 13, H-cadherin (heart)

SIPA1L2	ENZ	1	228,796,685	16	0.00040	signal-induced proliferation-associated 1 like 2
PDE4D	ENZ	5	58,461,253	4	0.00329	phosphodiesterase 4D, cAMP-specific (phosphodiesterase E3 dunce homolog, Drosophila)
PDE1C	ENZ	7	31,648,914	8	0.00204	phosphodiesterase 1C, calmodulin-dependent 70 kDa
PRKG1a	ENZ	10	52,485,930	5	0.00299	protein kinase, cGMP-dependent, type I
PRKG1b	ENZ	10	52,986,999	10	0.00214	protein kinase, cGMP-dependent, type I

ELMO1	PROT	7	36,840,767	9	0.00243	engulfment and cell motility 1 (ced-12 homolog, C. elegans)
MICALCL	PROT	11	12,241,526	7	0.00115	MICAL C-terminal like
IMPACT*	PROT	18	20,182,039	9	0.0007	hypothetical protein IMPACT

GRM7	REC	3	6,934,982	5	0.00289	glutamate receptor, metabotropic 7
GPR154*	REC	7	34,383,589	4	0.00123	G protein-coupled receptor 154
HRH4*	REC	18	20,280,986	9	0.0007	histamine receptor H4

NFIB	TF	9	14,190,005	6	0.00274	nuclear factor I/B

KCNQ3*	CHA	8	133,172,472	5	0.00114	potassium voltage-gated channel, KQT-like subfamily, member 3
				4
SLC9A9	TRANSP	3	144,947,291	12	0.00333	solute carrier family 9 (sodium/hydrogen exchanger), isoform 9
XKR5*	TRANSP	8	6,650,733	4	0.00063	XK, Kell blood group complex subunit-related family, member 5
ABCC4	TRANSP	13	94,600,083	5	0.0035	ATP-binding cassette, sub-family C (CFTR/MRP), member 4

PTHB1	DIS	7	33,369,755	21	0.00250	parathyroid hormone-responsive B1

ACTN2	STR	1	233,147,888	5	0.00016	actinin, alpha 2
OC90*	STR	8	133,172,472	5	0.00114	otoconin 90

HHLA1*	OTHER	8	133,172,472	12	0.00114	HERV-H LTR-associating 1
DEFB1*	OTHER	8	6,650,733	5	0.00063	defensin, beta 1
FGF14	OTHER	13	101,764,771	12	0.003	fibroblast growth factor 14
A2BP1	OTHER	16	6,603,645	9	0.00171	ataxin 2-binding protein 1
OSBPL1A	OTHER	18	20,182,039	11	0.0007	oxysterol binding protein-like 1A

Nicotine dependent vs control comparisons from the current work add support to previous addict vs control association observations in specific genes. Genes and classes of genes that contain nominally positive (p n = 139) and control (n = 320) individuals in the current study and enhance the significance of previously-obtained whole genome association results for addiction. To be included in this list, the data from the current comparison needs to improve the nominal significance of 100000 Monte Carlo simulation trials by > 10 trials when the current data is added to data from four prior samples. Four prior samples are comprised of genes previously nominated to play roles in addiction based on reproducible nominally positive allele frequency differences between European-American, African-American and Japanese individuals who are dependent on illegal substances or alcohol. Genes in this table this contain: 1) SNPs that display p vs controls in previous studies 3) SNPs that displayed p vs control individuals (COGA [55]) and 4) SNPs that displayed p vs control individuals (JGIDA [56]).
Genes are identified when positive SNPs lie 1) within the gene's exons or introns or 2) in 3' or 5' flanking sequences that lay within 100 Kb of an annotated exon or extensions of the currently-annotated exons as described [22]. Genes are grouped by the class of the function to which they contribute: "CAM" cell adhesion, "ENZ" enzymes, "PROT" protein processing, "REC" receptors, "TF" transcriptional regulation, "CHA" channels, "TRANSP" transporters, "DIS" disease associated, "STR" structural, "OTHER" other functions. Chromosome number and initial chromosomal position for the cluster (bp, NCBI Mapviewer Build 35.1) are listed. Monte Carlo p values come from 100,000 simulation trials. In each trial, randomly selected sequences lying within randomly selected gene sequences of the same length displayed by the actual genomic segments analyzed here were assessed to determine whether or not they contained at least the number of positive SNPs actually identified for each gene cluster and gene. The frequency of trials in which at least the observed numbers of nominally-positive SNPs were identified in each of the four samples studied here was recorded to provide an empirical p value. Several genes are identified by the same clusters of positive SNPs; these genes are indicated with asterisk symbols. Several genes, identified in several lines of Table 1, contain multiple clusters of reproducibly positive SNPs; the clusters are designated by suffixes a, b etc. We note that the requirements for nominally-significant association signals in each of five samples and increasing significance based on data from the current nicotine dependent vs control comparisons are likely to increase the number of false-negative results; interesting genes that receive support from only four samples are not listed here, for example.

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Table - Molecular genetics of nicotine dependence and abstinence: whole genome association using 520,000 SNPs

Table
- Molecular genetics of nicotine dependence and abstinence: whole genome association using 520,000 SNPs