Lung cancer in ever- and never-smokers: findings from multi-population GWAS studies.

BackgroundClinical, molecular, and genetic epidemiology studies displayed remarkable differences between ever- and never-smoking lung cancer.MethodsWe conducted a stratified multi-population (European, East Asian, and African descent) association study on 44,823 ever-smokers and 20,074 never-smokers to identify novel variants that were missed in the non-stratified analysis. Functional analysis including eQTL colocalization and DNA damage assays, and annotation studies were conducted to evaluate the functional roles of the variants. We further evaluated the impact of smoking quantity on lung cancer risk for the variants associated with ever-smoking lung cancer.ResultsFive novel independent loci, GABRA4, inter-genic region 12q24.33, LRRC4C, LINC01088, and LCNL1 were identified with the association at two or three populations (P 20). Different risk patterns were observed for the variants among the different groups by smoking behavior.ConclusionsWe identified novel variants associated with lung cancer in only ever- or never-smoking groups that were missed by prior main-effect association studies.ImpactOur study highlights the genetic heterogeneity between ever- and never-smoking lung cancer and provides etiological insights into the complicated genetic architecture of this deadly cancer

Figure S3 from Lung Cancer in Ever- and Never-Smokers: Findings from Multi-Population GWAS Studies

Supplementary Figure S3 displays the Validation of the association effect of rs6757077 at IKZF2 using data from six independent study sites in China.</p

Supplementary Table S8 from Lung Cancer in Ever- and Never-Smokers: Findings from Multi-Population GWAS Studies

Supplementary Table S8 displays the sample size from independent Asian studies.</p

Supplementary Table S5 from Lung Cancer in Ever- and Never-Smokers: Findings from Multi-Population GWAS Studies

Supplementary Table S5 shows the signals for the variants in stratified analysis by smoking behavior</p

Supplementary Table S3 from Lung Cancer in Ever- and Never-Smokers: Findings from Multi-Population GWAS Studies

Supplementary Table S3 shows the signals at rs7985487 in Firth test validation.</p

Figure S4 from Lung Cancer in Ever- and Never-Smokers: Findings from Multi-Population GWAS Studies

Supplementary Figure S4 shows the results of eQTL analysis of rs968516 in GTEx.</p

Supplementary Table S7 from Lung Cancer in Ever- and Never-Smokers: Findings from Multi-Population GWAS Studies

Supplementary Table S7 shows the signals from interaction with smoking status for the identified variants in lung cancer.</p

Figure S1 from Lung Cancer in Ever- and Never-Smokers: Findings from Multi-Population GWAS Studies

Supplementary Figure S1 displays the distribution of histology subtypes in each population in ever- and never-smokers.</p

Supplementary Table S6 from Lung Cancer in Ever- and Never-Smokers: Findings from Multi-Population GWAS Studies

Supplementary Table S6 displays epigenomic evidence for the variants being located within genomic regions associated with regulatory activity.</p

Supplementary Table S1 from Lung Cancer in Ever- and Never-Smokers: Findings from Multi-Population GWAS Studies

Supplementary Table S1 displays the number of ever- and never-smokers from each of the ten studies.</p