A genome‐wide screen for nicotine dependence susceptibility loci

Swan, Gary E.; Hops, Hyman; Wilhelmsen, Kirk C.; Lessov‐Schlaggar, Christina N.; Li, Cheng; Hudmon, Karen Suchanek; Amos, Christopher I.; Feiler, Heidi S.; Ring, Huijun Z.; Andrews, Judy A.; Tildesley, Elizabeth; Benowitz, Neal L.

doi:10.1002/ajmg.b.30315

Cited by 61 publications

(61 citation statements)

References 58 publications

(68 reference statements)

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“…155,156 OPRM1 is located in chromosome 6q24-q25 and this region was recently linked to FTND scores and withdrawal severity (Table 1). 39 Further, high doses of the opiate antagonist naltrexone, in combination with NRT patch, increased continuous abstinence compared to NRT patch alone. 157 Some studies, although not all, have found an association between the A118G variant and opiate or alcohol addiction (reviewed by Mayer and Hollt 158 ).…”

Section: Other Likely Candidates Involved In Neurotransmitter Systemsmentioning

confidence: 98%

“…A wide variety of smoking phenotypes have been investigated (Table 1), however only two genome-wide scans using direct measures of ND have been published. [37][38][39] Some of the loci associated with ND are near genes of known biological relevance, including the m 1 -opioid receptor (OPRM1) on chromosome 6, serotonin receptor 5A on chromosome 7 as well as a 2 -nicotinic acetylcholine receptor (CHRNA2) and a 1A -adrenergic receptor (ADRA1A) on chromosome 8. 39 Loci identified with other smoking phenotypes also contain some biologically interesting candidates, such as a region on chromosome 5q located near the dopamine receptor (D 1 ) gene, which has been reported in several studies.…”

Section: Genome-wide Linkage Studiesmentioning

confidence: 99%

“…[37][38][39] Some of the loci associated with ND are near genes of known biological relevance, including the m 1 -opioid receptor (OPRM1) on chromosome 6, serotonin receptor 5A on chromosome 7 as well as a 2 -nicotinic acetylcholine receptor (CHRNA2) and a 1A -adrenergic receptor (ADRA1A) on chromosome 8. 39 Loci identified with other smoking phenotypes also contain some biologically interesting candidates, such as a region on chromosome 5q located near the dopamine receptor (D 1 ) gene, which has been reported in several studies. 32,40,41 Regions on chromosomes 6, 9 and 11 26,32,33,[40][41][42][43][44][45][46] are also promising as several studies have replicated the linkage and these regions contain some potential biologically relevant candidate genes (Table 1).…”

Section: Genome-wide Linkage Studiesmentioning

confidence: 99%

“…173 CYP2A6 is located on chromosome 19 (19q13.2) and a nearby region was associated with smoking frequency (X1 cigarette per day) in a genome-wide linkage scan. 39 Large interindividual and interethnic variations in CYP2A6 activity have been reported; [170][171][172][174][175][176][177] this variability is mainly attributed to the large genetic variations in CYP2A6. 178,179 A brief summary of how genetic variations in CYP2A6 affect smoking behaviors will be provided here as a detailed review was recently published.…”

Section: Other Likely Candidates Involved In Neurotransmitter Systemsmentioning

confidence: 99%

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Overview of the pharmacogenomics of cigarette smoking

Tyndale

2007

Pharmacogenomics J

102

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Cigarette smoking increases the risk of numerous health problems, including cancer, cardiovascular and pulmonary disorders, making smoking the leading cause of preventable death in the world. Nicotine is primarily responsible for the highly addictive properties of cigarettes. Although the majority of smokers express a desire to quit, few are successful in doing so. Twin and family studies have indicated substantial genetic contributions to smoking behaviors. One major research focus has been to elucidate the specific genes involved; this has been accomplished primarily through genome-wide linkage analyses and candidate gene association studies. Much attention has focused on genes involved in the neurotransmitter pathways for the brain reward system and genes altering nicotine metabolism. This paper reviews the current state of knowledge for genetic factors implicated in smoking behaviors, and examines how genetic variations may affect therapeutic outcomes for drugs used to assist smoking cessation.

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Section: Other Likely Candidates Involved In Neurotransmitter Systemsmentioning

confidence: 98%

Section: Genome-wide Linkage Studiesmentioning

confidence: 99%

Section: Genome-wide Linkage Studiesmentioning

confidence: 99%

Section: Other Likely Candidates Involved In Neurotransmitter Systemsmentioning

confidence: 99%

See 2 more Smart Citations

Overview of the pharmacogenomics of cigarette smoking

Tyndale

2007

Pharmacogenomics J

102

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“…However, ascertainment criteria as well as study samples have been diverse, and not surprisingly, only a few findings seem consistent across studies. Depending on the study population and the phenotype criteria used, some evidence of linkage (logarithm of the odds (LOD)/Z scores X2) for ND has been reported on chromosomes 2, 6, 7, 8, 10, 11 and 18, [10][11][12][13] linkage for smoking rate on chromosomes 3, 4, 5, 10, 11 and 17, 7,[12][13][14][15][16] and linkage for ever smoking, habitual smoking or smoking initiation on chromosomes 6, 9 and 11. 7,[16][17][18] Thus, suggestive findings for smoking-related loci exist for most chromosomes.…”

Section: Introductionmentioning

confidence: 99%

Linkage of nicotine dependence and smoking behavior on 10q, 7q and 11p in twins with homogeneous genetic background

et al. 2007

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The significant worldwide health burden introduced by tobacco smoking highlights the importance of studying the genetic determinants of smoking behavior and the key factor sustaining compulsive smoking, that is, nicotine dependence (ND). We have here addressed the genetic background of smoking in a special study sample of twins, harmonized for early life events and specifically ascertained for smoking from the nationwide twin cohort of the genetically unique population of Finland. The twins and their families were carefully examined for extensive phenotype profiles and a genomewide scan was performed to identify loci behind the smoking status, ND and the comorbid phenotype of ND and alcohol use in 505 individuals from 153 families. We replicated previous linkage findings on 10q (max logarithm of the odds (LOD) 3.12) for a smoker phenotype, and on 7q and 11p (max LOD 2.50, and 2.25, respectively) for the ND phenotype. The loci linked for ND also showed evidence for linkage for the comorbid phenotype. Our study provides confirmatory evidence for the involvement of these genome regions in the genetic etiology of smoking behavior and ND and for the first time associates drinking and smoking to a shared locus on 10q.

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Cannabinoid Receptor 1 Gene Association With Nicotine Dependence

Chen

Williamson²,

An³

et al. 2008

Arch Gen Psychiatry

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Context The endogenous cannabinoid system has been implicated in drug addiction in animal models. The cannabinoid receptor 1 (CNR1) gene is 1 of the 2 receptors expressed in the brain. It has been reported to be associated with alcoholism and multiple drug abuse and dependence. Objective To test the hypothesis that the CNR1 gene is associated with nicotine dependence. Design Genotype-phenotype association study. Ten single-nucleotide polymorphisms were genotyped in the CNR1 gene in 2 independent samples. For the first sample (n=688), a 3-group case-control design was used to test allele association with smoking initiation and nicotine dependence. For the second sample (n = 961), association was assessed with scores from the Fagerström Test for Nicotine Dependence (FTND). Settings Population samples selected from the Mid-Atlantic Twin Registry. Participants White patients aged 18 to 65 years who met the criteria of inclusion. Main Outcome Measures Fagerström Tolerance Questionnaire and FTND scores. Results Significant single-marker and haplotype associations were found in both samples, and the associations were female specific. Haplotype 1-1-2 of markers rs2023239-rs12720071-rs806368 was associated with nicotine dependence and FTND score in the 2 samples (P<.001 and P = .009, respectively). Conclusion Variants and haplotypes in the CNR1 gene may alter the risk for nicotine dependence, and the associations are likely sex specific.

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A genome‐wide screen for nicotine dependence susceptibility loci

Cited by 61 publications

References 58 publications

Overview of the pharmacogenomics of cigarette smoking

Overview of the pharmacogenomics of cigarette smoking

Linkage of nicotine dependence and smoking behavior on 10q, 7q and 11p in twins with homogeneous genetic background

Cannabinoid Receptor 1 Gene Association With Nicotine Dependence

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