Multiple Independent Loci at Chromosome 15q25.1 Affect Smoking Quantity: a Meta-Analysis and Comparison with Lung Cancer and COPD

@article{Saccone2010MultipleIL,
  title={Multiple Independent Loci at Chromosome 15q25.1 Affect Smoking Quantity: a Meta-Analysis and Comparison with Lung Cancer and COPD},
  author={Nancy L. Saccone and Robert C Culverhouse and Tae‐Hwi Schwantes‐An and Dale S. Cannon and Xiangning Chen and Sven Cichon and Ina Giegling and Shizhong Han and Younghun Han and Kaisu Keskitalo-Vuokko and Xiangyang Kong and Maria Teresa Landi and Jennie Z. Ma and Susan E. Short and Sarah H. Stephens and Victoria L. Stevens and Lingwei Sun and Yufei Wang and Angela S. Wenzlaff and Steven H. Aggen and Naomi Breslau and Peter Broderick and Nilanjan Chatterjee and Jingchun Chen and Andrew C. Heath and Markku Heli{\"o}vaara and Nicole R. Hoft and David J. Hunter and Majken K. Jensen and Nicholas G. Martin and Grant W. Montgomery and Tianhua Niu and Thomas J. Payne and Leena Peltonen and Michele L. Pergadia and John P. Rice and Richard Sherva and Margaret R. Spitz and Juzhong Sun and Jen C. Wang and Robert B. Weiss and William Wheeler and Stephanie H. Witt and Bao-Zhu Yang and Neil E. Caporaso and Marissa A Ehringer and Timothy Eisen and Susan M Gapstur and Joel Gelernter and Richard S. Houlston and Jaakko A Kaprio and Kenneth S. Kendler and Peter Kraft and M. Leppert and Ming D. Li and Pamela A. F. Madden and Markus M. N{\"o}then and Sreekumar G Pillai and Marcella Rietschel and Dan Rujescu and Ann G. Schwartz and Christopher I. Amos and Laura J. Bierut},
  journal={PLoS Genetics},
  year={2010},
  volume={6}
}
Recently, genetic association findings for nicotine dependence, smoking behavior, and smoking-related diseases converged to implicate the chromosome 15q25.1 region, which includes the CHRNA5-CHRNA3-CHRNB4 cholinergic nicotinic receptor subunit genes. In particular, association with the nonsynonymous CHRNA5 SNP rs16969968 and correlates has been replicated in several independent studies. Extensive genotyping of this region has suggested additional statistically distinct signals for nicotine… 
Association between a 15q25 gene variant, nicotine-related habits, lung cancer and COPD among 56 307 individuals from the HUNT study in Norway
TLDR
A role for rs16969968 in nicotine addiction is suggested, and the novel association with snus strengthens this observation.
Genetic variants on 15q25.1, smoking, and lung cancer: an assessment of mediation and interaction.
TLDR
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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 andYoung adults.
CHRNA5 risk variant predicts delayed smoking cessation and earlier lung cancer diagnosis--a meta-analysis.
TLDR
Data support the clinical significance of the CHRNA5 variant rs16969968, which predicts delayed smoking cessation and an earlier age of lung cancer diagnosis in this meta-analysis, and underscore the potential clinical and public health importance of this variant.
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TLDR
This study confirmed both rs6495308 and rs11072768 gene polymorphisms association with smoking behaviors and had an indirect link between gene polymorphism and lung cancer risk.
Role of CHRNA5-A3 genetic Locus variants and developing drug for chronic obstructive pulmonary disease.
TLDR
Genome-wide association studies both in lung cancer and COPD highlighted the same variants (SNPs) on chromosome 15q25 marking the gene cluster CHRNA3-CHRNB4-CHRNA5 for these smoking related diseases, showing a stimulating connection between this common genetic region and smoking behavior and smoking related illnesses.
Chr15q25 genetic variant (rs16969968) independently confers risk of lung cancer, COPD and smoking intensity in a prospective study of high-risk smokers
TLDR
The CHRNA5 rs 16 969 968 AA genotype was found to be independently associated with smoking exposure, COPD and lung cancer (triple whammy effect) in this large-prospective study.
Association of the CHRNA5-A3-B4 Gene Cluster With Heaviness of Smoking: A Meta-Analysis
TLDR
Meta-analysis indicated compelling evidence of an association between the rs1051730/rs16966968 variants and daily cigarette consumption and may be a strong tagging SNP for functional haplotypes in this region.
Association between Genetic Variants on Chromosome 15q25 Locus and Several Nicotine Dependence Traits in Polish Population: A Case-Control Study
TLDR
Strong evidence is provided for the role of the CHRNA5-CHRNA3-CHRNB4 cluster in heaviness of nicotine addiction.
Contribution of Variants in CHRNA5/A3/B4 Gene Cluster on Chromosome 15 to Tobacco Smoking: From Genetic Association to Mechanism
TLDR
An up-to-date review of the progress of studies focusing on the CHRNA5/A3/B4 gene cluster and its role in ND is provided.
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