Abstract
Smoking is a major public health problem, but the genetic factors associated with smoking behaviors are not fully elucidated. Here, we have conducted an integrated genome-wide association study to identify common copy number polymorphisms (CNPs) and single nucleotide polymorphisms (SNPs) associated with the number of cigarettes smoked per day (CPD) in Japanese smokers ( = 17,158). Our analysis identified a common CNP with a strong effect on CPD (rs8102683; ) in the 19q13 region, encompassing the CYP2A6 locus. After adjustment for the associated CNP, we found an additional associated SNP (rs11878604; ) located 30 kb downstream of the CYP2A6 gene. Imputation of the CYP2A6 locus revealed that haplotypes underlying the CNP and the SNP corresponded to classical, functional alleles of CYP2A6 gene that regulate nicotine metabolism and explained 2% of the phenotypic variance of CPD (ANOVA -test ). These haplotypes were also associated with smoking-related diseases, including lung cancer, chronic obstructive pulmonary disease and arteriosclerosis obliterans.
Highlights
Smoking is a common risk factor for many diseases and a leading cause of mortality [1]
Genomewide association studies (GWAS) and genome-wide meta-analyses have identified several genetic loci that are associated with smoking quantity, smoking initiation, smoking cessation and age of smoking initiation [4,5,6]
Each copy number polymorphisms (CNPs) or single-nucleotide polymorphisms (SNPs) was evaluated for association with cigarettes smoked per day (CPD) using a linear regression model that accounted for the additive effects of copy number dosage or allele dosage on CPD with other covariates
Summary
Smoking is a common risk factor for many diseases and a leading cause of mortality [1]. Genomewide association studies (GWAS) and genome-wide meta-analyses have identified several genetic loci that are associated with smoking quantity (as estimated by the number of cigarettes smoked per day, CPD), smoking initiation, smoking cessation and age of smoking initiation [4,5,6]. These studies were conducted in subjects of European descent, and few GWAS have been performed in any Asian population, even though this group accounts for two-thirds of the world population. Our study estimated the heritability explained by the haplotype for CPD and smoking-related disease traits
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
