Genetic architecture of four smoking behaviors using partitioned SNP heritability

Abstract

Background and Aims Although genome-wide association studies have identified many loci that influence smoking behaviors, much of the genetic variance remains unexplained. We characterized the genetic architecture of four smoking behaviors using single nucleotide polymorphism (SNP) heritability (h(SNP)(2)). This is an estimate of narrow-sense heritability specifically estimating the proportion of phenotypic variation due to causal variants (CVs) tagged by SNPs.Design Partitioned h(SNP)(2) analysis of smoking behavior traits.Setting UK Biobank.Participants UK Biobank participants of European ancestry. The number of participants varied depending on the trait, from 54 792 to 323 068.Measurements Smoking initiation, age of initiation, cigarettes per day (CPD; count, log-transformed, binned and dichotomized into heavy versus light) and smoking cessation with imputed genome-wide SNPs.Findings We estimated that, in aggregate, approximately 18% of the phenotypic variance in smoking initiation was captured by imputed SNPs [h(SNP)(2) = 0.18, standard error (SE) = 0.01] and 12% [SE = 0.02] for smoking cessation, both of which were more than twice the previously reported estimates. Estimated age of initiation (h(SNP)(2) = 0.05, SE = 0.01) and binned CPD (h(SNP)(2) = 0.1, SE = 0.01) were substantially below published twin-based h(2) of 50%. CPD encoding influenced estimates, with dichotomized CPD h(SNP)(2) = 0.28. There was no evidence of dominance genetic variance for any trait.Conclusion A biobank study of smoking behavior traits suggested that the phenotypic variance explained by SNPs of smoking initiation, age of initiation, cigarettes per day and smoking cessation is modest overall.