BackgroundSmoking is the principal modifiable environmental risk factor for chronic obstructive pulmonary disease (COPD) which affects 300 million people and is the 3rd leading cause of death worldwide. Most of the genetic studies of smoking have relied on self-reported smoking status which is vulnerable to reporting and recall bias. Using data from the Lung Health Study (LHS), we sought to identify genetic variants associated with quantitative smoking and cessation in individuals with mild to moderate COPD.MethodsThe LHS is a longitudinal multicenter study of mild-to-moderate COPD subjects who were all smokers at recruitment. We performed genome-wide association studies (GWASs) for salivary cotinine (n = 4024), exhaled carbon monoxide (eCO) (n = 2854), cigarettes per day (CPD) (n = 2706) and smoking cessation at year 5 follow-up (n = 717 quitters and 2175 smokers). The GWAS analyses were adjusted for age, gender, and genetic principal components.ResultsFor cotinine levels, SNPs near UGT2B10 gene achieved genome-wide significance (i.e. P < 5 × 10− 8) with top SNP rs10023464, P = 1.27 × 10− 11. For eCO levels, one significant SNP was identified which mapped to the CHRNA3 gene (rs12914385, P = 2.38 × 10− 8). A borderline region mapping to KCNMA1 gene was associated with smoking cessation (rs207675, P = 5.95 × 10− 8). Of the identified loci, only the CHRNA3/5 locus showed significant associations with lung function but only in heavy smokers. No regions met genome-wide significance for CPD.ConclusionThe study demonstrates that using objective measures of smoking such as eCO and/or salivary cotinine can more precisely capture the genetic contribution to multiple aspects of smoking behaviour. The KCNMA1 gene association with smoking cessation may represent a potential therapeutic target and warrants further studies.Trial registrationThe Lung Health Study ClinicalTrials.gov Identifier: NCT00000568. Date of registration: October 28, 1999.Electronic supplementary materialThe online version of this article (10.1186/s12931-018-0762-7) contains supplementary material, which is available to authorized users.