Variants located upstream of CHRNB4 on chromosome 15q25.1 are associated with age at onset of daily smoking and habitual smoking.
- Authors
- Kapoor, Manav; Wang, Jen-Chyong; Bertelsen, Sarah; Bucholz, Kathy; Budde, John P; Hinrichs, Anthony; Agrawal, Arpana; Brooks, Andrew; Chorlian, David; Dick, Danielle; Hesselbrock, Victor; Foroud, Tatiana; Kramer, John; Kuperman, Samuel; Manz, Niklas; Nurnberger, John; Porjesz, Bernice; Rice, John; Tischfield, Jay; Xuei, Xiaoling; Schuckit, Marc; Edenberg, Howard J; Bierut, Laura J; Goate, Alison M
- Year
- 2012
- Journal
- PloS one
- PMID
- 22438940
- DOI
- 10.1371/journal.pone.0033513
- PMCID
- PMC3306405
Several genome-wide association and candidate gene studies have linked chromosome 15q24-q25.1 (a region including the CHRNA5-CHRNA3-CHRNB4 gene cluster) with alcohol dependence, nicotine dependence and smoking-related illnesses such as lung cancer and chronic obstructive pulmonary disease. To further examine the impact of these genes on the development of substance use disorders, we tested whether variants within and flanking the CHRNA5-CHRNA3-CHRNB4 gene cluster affect the transition to daily smoking (individuals who smoked cigarettes 4 or more days per week) in a cross sectional sample of adolescents and young adults from the COGA (Collaborative Study of the Genetics of Alcoholism) families. Subjects were recruited from families affected with alcoholism (either as a first or second degree relative) and the comparison families. Participants completed the SSAGA interview, a comprehensive assessment of alcohol and other substance use and related behaviors. Using the Quantitative trait disequilibrium test (QTDT) significant association was detected between age at onset of daily smoking and variants located upstream of CHRNB4. Multivariate analysis using a Cox proportional hazards model further revealed that these variants significantly predict the age at onset of habitual smoking among daily smokers. These variants were not in high linkage disequilibrium (0.28<r(2)<0.56) with variants that have previously been reported to affect risk for nicotine dependence and smoking related diseases in adults. The data suggests that an age-associated relationship underlies the association of SNPs in CHRNB4 with onset of chronic smoking behaviors in adolescents and young adults and may improve genetic information that will lead to better prevention and intervention for substance use disorders among adolescents and young adults.
Genotypes of rs1996371 significantly predict age at onset of habitual smoking.
Linkage disequilibrium between genotyped SNPs.Number in each square represents the a pairwise LD relationship (r2) between the two SNP's in Caucasians using HapMap data and varying red color represent the linkage disequilibrium values for that pair as measured by Dβ² (bright red shows high Dβ²).
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External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Genetic influences impacting nicotine use and abuse during adolescence: Insights from human and rodent studies. | Goldberg LR et al. | β | 2022 | β |
| A 5-Factor Framework for Assessing Tobacco Use Disorder. | Bucklin M | β | 2021 | β |
| Nicotinic Receptors Underlying Nicotine Dependence: Evidence from Transgenic Mouse Models. | Gipson CD et al. | β | 2020 | β |
| CYP2A6 metabolism in the development of smoking behaviors in young adults. | Olfson E et al. | β | 2018 | β |
| Neuroepigenetics and addiction. | Walker DM et al. | β | 2018 | β |
| Mechanisms and genetic factors underlying co-use of nicotine and alcohol or other drugs of abuse. | Cross SJ et al. | β | 2017 | β |
| Nicotinic acetylcholine receptors: upregulation, age-related effects and associations with drug use. | Melroy-Greif WE et al. | β | 2016 | β |
| Small Heat Shock Proteins Are Novel Common Determinants of Alcohol and Nicotine Sensitivity in Caenorhabditis elegans. | Johnson JR et al. | β | 2016 | β |
| Unsupervised text mining for assessing and augmenting GWAS results. | Ailem M et al. | β | 2016 | β |
| Differential expression of the beta4 neuronal nicotinic receptor subunit affects tolerance development and nicotinic binding sites following chronic nicotine treatment. | Meyers EE et al. | β | 2015 | β |
| Genetic risks to nicotine dependence predict negative mood and affect in current non-smokers. | Chen X et al. | β | 2015 | β |
| Pharmacogenetics of nicotine and associated smoking behaviors. | Tanner JA et al. | β | 2015 | β |
| Response to Transdermal Selegiline Smoking Cessation Therapy and Markers in the 15q24 Chromosomal Region. | Sarginson JE et al. | β | 2015 | β |
| ADHD diagnosis may influence the association between polymorphisms in nicotinic acetylcholine receptor genes and tobacco smoking. | Polina ER et al. | β | 2014 | β |
| Beyond GWAS in COPD: probing the landscape between gene-set associations, genome-wide associations and protein-protein interaction networks. | McDonald ML et al. | β | 2014 | β |
| Genetics and smoking. | Loukola A et al. | β | 2014 | β |
| Habenular expression of rare missense variants of the Ξ²4 nicotinic receptor subunit alters nicotine consumption. | Slimak MA et al. | β | 2014 | β |
| Alternative CHRNB4 3'-UTRs mediate the allelic effects of SNP rs1948 on gene expression. | Gallego X et al. | β | 2013 | β |
| Current genetics and epigenetics of smoking/tobacco-related cardiovascular disease. | Breitling LP | β | 2013 | β |
| Substance abuse precedes Internet addiction. | Lee YS et al. | β | 2013 | β |
| Current perspectives on the neurobiology of drug addiction: a focus on genetics and factors regulating gene expression. | Duncan JR | β | 2012 | β |