Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). SNV-trait associations with P < 5 × 10−8 in either analysis were taken forward for replication in up to 275,596 independent participants from UK Biobank. Lastly, a meta-analysis of the discovery and replication studies was performed. These novel loci will facilitate understanding the genetic aetiology of smoking behaviour and may lead to the identification of potential drug targets for smoking prevention and/or cessation.
Here we have included four sets of meta-analysis results: Meta-analysis of discovery and replication cohorts, combining genotyped Exome-chip and Axiom array content for (i) Smoking Initiation, (ii) Cigarettes per day, and (iii) Smoking Cessation, and (iv) meta-analysis of discovery cohorts for Pack Years.
Erzurumluoglu, A. M., Liu, M., Jackson, V. E., Barnes, D. R., Datta, G., Melbourne, C. A., … Understanding Society Scientific Group, E.-C., GSCAN, Consortium for Genetics of Smoking Behaviour, CHD Exome+ consortium. (2019). Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci. Molecular Psychiatry.