Skip to main content

Advertisement

Table 1 Nicotine dependent vs control comparisons

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

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
  1. 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 < 0.005) SNPs in comparisons between nicotine dependent(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 < 0.005 significance for differences between nicotine dependent and control individuals in the present study 2) clustered SNPs that displayed significant (p < 0.05) differences between both European-American and African-American NIDA polysubstance abusers vs controls in previous studies 3) SNPs that displayed p < 0.05 significance in 100k association genome scans of alcohol dependent vs control individuals (COGA [55]) and 4) SNPs that displayed p < 0.05 significance in 100k association genome scans of methamphetamine dependent vs control individuals (JGIDA [56]).
  2. 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.