Results of a genomewide linkage scan: Support for chromosomes 9 and 11 loci increasing risk for cigarette smoking

Gelernter, Joel; Liu, Xuexuan; Hesselbrock, Victor; Page, Grier P.; Goddard, Andrew W.; Zhang, Huiping

doi:10.1002/ajmg.b.30019

Cited by 82 publications

(80 citation statements)

References 31 publications

(46 reference statements)

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“…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%

“…65,66 A 48-bp variable number tandem repeat (VNTR) in exon 3 of DRD4 has also been of interest; genome-wide linkage analyses have implicated a region on chromosome 11p15.5 near DRD4 with habitual smoking (Table 1). 45 In African Americans, but not Caucasians, the long (L) allele (containing Table 2 Summary of studies examining TaqI A polymorphism in DRD2 and smoking behaviors Phenotype Population Association References…”

Section: Mk Ho and Rf Tyndale 86mentioning

confidence: 99%

“…68 Examination of a single-nucleotide polymorphism (SNP) in the 3 0 -UTR of SCL6A3-9 (rs27072G4A) found individuals with the A-allele were more likely to initiate smoking before age 18 years. 98 Dopamine metabolism TH encodes tyrosine hydroxylase, the rate-limiting enzyme for the synthesis of dopamine, and a region near this gene on chromosome 11p15.5 has been implicated with habitual smoking in genome-wide linkage scans 45 (Table 1). 45 A fournucleotide VNTR polymorphism (HUMTH01-VNTR) in intron 1 is postulated to affect gene expression, as it resides in a region where numerous transcription factors bind.…”

Section: Dopamine Transportermentioning

confidence: 99%

“…98 Dopamine metabolism TH encodes tyrosine hydroxylase, the rate-limiting enzyme for the synthesis of dopamine, and a region near this gene on chromosome 11p15.5 has been implicated with habitual smoking in genome-wide linkage scans 45 (Table 1). 45 A fournucleotide VNTR polymorphism (HUMTH01-VNTR) in intron 1 is postulated to affect gene expression, as it resides in a region where numerous transcription factors bind. 99 Adolescent smokers with the four-repeat allele (K4) were less likely to be ND compared to those with 1-3 (K1-K3) or five repeats (K5) alleles.…”

Section: Dopamine Transportermentioning

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: Genome-wide Linkage Studiesmentioning

confidence: 99%

Section: Mk Ho and Rf Tyndale 86mentioning

confidence: 99%

Section: Dopamine Transportermentioning

confidence: 99%

Section: Dopamine Transportermentioning

confidence: 99%

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Overview of the pharmacogenomics of cigarette smoking

Tyndale

2007

Pharmacogenomics J

102

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“…In other investigations of interest to the current study, cigarette smoking with or without AD, were linked to broad regions of chromosomes 9 and 11. [4][5][6][7][8][9] Among the candidate addiction susceptibility genes defined by these linkage signals were those that encode the neurotrophin, brainderived neurotrophic factor (BDNF, chromosome 11), and its cognate receptor, neurotrophic tyrosine kinase receptor B (TrkB) (NTRK2, chromosome 9).…”

Section: Introductionmentioning

confidence: 99%

Nucleotide sequence variation within the human tyrosine kinase B neurotrophin receptor gene: association with antisocial alcohol dependence

Anderson

Neyer

et al. 2007

Pharmacogenomics J

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To identify sequence variants in genes that may have roles in neuronal responses to alcohol, we resequenced the 5 0 region of tyrosine kinase B neurotrophin receptor gene (NTRK2) and determined linkage disequilibrium (LD) values, haplotype structure, and performed association analyses using 43 single nucleotide polymorphisms (SNPs) covering the entire NTRK2 region in a Finnish Caucasian sample of 229 alcohol-dependent subjects with antisocial personality disorder (ASPD) and 287 healthy controls. Individually, three SNPs were associated with alcohol dependence and alcohol abuse (AD) (P-value from 0.0019 to 0.0059, significance level was set at Pp0.01 corrected for multiple testing), whereas a common 18 locus haplotype within the largest LD block of NTRK2, a 119-kb region containing the 5 0 flanking region and exons 1-15, was marginally overrepresented in control subjects compared to AD individuals (global P ¼ 0.057). Taken together, these results support a role for the NTRK2 gene in addiction in a Caucasian population with AD and a subtype of ASPD.

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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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Results of a genomewide linkage scan: Support for chromosomes 9 and 11 loci increasing risk for cigarette smoking

Cited by 82 publications

References 31 publications

Overview of the pharmacogenomics of cigarette smoking

Overview of the pharmacogenomics of cigarette smoking

Nucleotide sequence variation within the human tyrosine kinase B neurotrophin receptor gene: association with antisocial alcohol dependence

Cannabinoid Receptor 1 Gene Association With Nicotine Dependence

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