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. 2023 Apr 20;12:e83118. doi: 10.7554/eLife.83118

Figure 1. Genetic correlations between leukocyte telomere length (LTL) and lung cancer (LC) related traits.

(A) Heatmap representing the genetic correlation analyses (rg) for LTL across LC, histological subtypes (lung adenocarcinoma [ADE], squamous cell carcinoma [SQC], and small-cell carcinoma [SCC]), smoking propensity (cigarettes per day [CPD], smoking cessation [SmkCes], Smoking initiation [SmkInit], and age of smoking initiation [AgeSmk]), and lung function related (forced vital capacity [FVC] and forced expiratory volume [FEV1]) traits. The black star indicates correlations that passed Bonferroni correction (p<4x10–04). Heritability (h2) as the proportion of the phenotypic variance caused by SNPs. (B) Plot of Z-scores (ADE versus LTL), restricting to the Hapmap SNPs (~1.2 million) but excluding HLA region. Genome-wide significant SNPs (p<5x10–08) for each trait were coloured (CPD in red, SmkInit in dark red, LTL in dark blue, AgeSmk in blue, SmkCes in lightblue, and not genome-wide hits for LTL or any other selected trait in white). Linear regression line was coloured in red.

Figure 1.

Figure 1—figure supplement 1. Design of the study.

Figure 1—figure supplement 1.

Upper: the leukocyte telomere length (LTL) variants were derived from the latest genome-wide association study (GWAS) in UK Biobank (UKBB) participants by Codd et al. Genome-wide correlations between LTL and lung cancer related traits were performed. Focus on a subset of LTL variants selected for Mendelian randomisation (MR) framework. Middle: selection of independent SNPs as LTL instrument for causal inference of LTL on lung cancer risk. Explore biological meaning of these variants using colocalisation methods and principal component analyses to summarise gene expression data. Bottom: calculate LTL polygenic risk score (PRS) based on the 144 SNPs and evaluate its association with principal components and epidemiological, and molecular data of lung adenocarcinoma tumours from The Cancer Genome Atlas (TCGA) dataset (TCGA-lung adenocarcinoma [LUAD]).