Additional file 2 of Systematic proteome-wide Mendelian randomization using the human plasma proteome to identify therapeutic targets for lung adenocarcinoma

Additional file 2. Table S1. Genetic instruments of plasma proteins for MR analysis. MR: Mendelian randomization; SNP: single nucleotide polymorphism; chr: chromosome; pos: position; eaf: effect allele frequency; se: standard error. Table S2. MR results for plasma proteins significantly associated with LUAD after Bonferroni correction. MR: Mendelian randomization; LUAD: lung adenocarcinoma; SNP: single nucleotide polymorphism; OR: odds ratio; CI: confidence interval; PVE: proportion of variance explained. Table S3. MR results of proteome and LUAD. MR: Mendelian randomization; LUAD: lung adenocarcinoma; SNP: single nucleotide polymorphism; nSNPs: number of SNPs; se: standard error; OR: odds ratio; CI: confidence interval; IVW:inverse-variance-weighted. Table S4. Steiger filtering and reverse MR results of LUAD as exposure and proteome as outcome. MR: Mendelian randomization; LUAD: lung adenocarcinoma; SNP: single nucleotide polymorphism; nSNPs: number of SNPs; OR: odds ratio; CI: confidence interval; IVW:inversevariance-weighted. Table S5. Bayesian co-localization analysis on nine potential causal proteins. Druggable genes were divided into three tiers, including targets of approved drugs and drugs in clinical development (tier 1), proteins closely related to drug targets or with associated drug-like compounds (tier 2), and extracellular proteins and members of key drug-target families (tier 3). SNP: single nucleotide polymorphism. Table S6. Previously-reported genome-wide significant association of SNPs as genetic instruments of three potential causal proteins. SNP: single nucleotide polymorphism; chr: chromosome; se: standard error; N_samples: number of samples; N_cases: number of cases; N_controls: number of controls. Table S7. MR results of risk factors versus LUAD (GWAS from European population). MR: Mendelian randomization; LUAD: lung adenocarcinoma; GWAS: genome-wide association study; SNP: single nucleotide polymorphism; nSNPs: number of SNPs; se: standard error; OR: odds ratio; CI: confidence interval; IVW:inverse-variance-weighted. Table S8. MR results of proteome and LUAD risk factors. MR: Mendelian randomization; LUAD: lung adenocarcinoma; SNP: single nucleotide polymorphism; nSNPs: number of SNPs; se: standard error; OR: odds ratio; CI: confidence interval; IVW:inverse-variance-weighted; COPD: chronic obstructive pulmonary disease. Table S9. LUAD mediation results for protein targets on LUAD via risk factors. LUAD: lung adenocarcinoma. Table S10. Summary of druggability and drug development for LUAD associated with plasma proteins through MR analysis. Druggable genes were divided into three tiers, including targets of approved drugs and drugs in clinical development (tier 1), proteins closely related to drug targets or with associated drug-like compounds (tier 2), and extracellular proteins and members of key drug-target families (tier 3). LUAD: lung adenocarcinoma; NSCLC: non-small cell lung cancer.

附加文件2 表S1：用于孟德尔随机化（Mendelian randomization, MR）分析的血浆蛋白遗传工具。注：MR即孟德尔随机化；SNP即单核苷酸多态性（single nucleotide polymorphism）；chr为染色体（chromosome）的缩写；pos为位置（position）的缩写；eaf为效应等位基因频率（effect allele frequency）的缩写；se为标准误（standard error）的缩写。表S2：经Bonferroni校正后与肺腺癌（lung adenocarcinoma, LUAD）显著相关的血浆蛋白的孟德尔随机化分析结果。注：MR即孟德尔随机化；LUAD即肺腺癌；SNP即单核苷酸多态性；OR为比值比（odds ratio）的缩写；CI为置信区间（confidence interval）的缩写；PVE为方差解释比例（proportion of variance explained）的缩写。表S3：蛋白质组与肺腺癌（LUAD）的孟德尔随机化分析结果。注：MR即孟德尔随机化；LUAD即肺腺癌；SNP即单核苷酸多态性；nSNPs为单核苷酸多态性数量的缩写；se为标准误；OR为比值比；CI为置信区间；IVW为逆方差加权（inverse-variance-weighted）的缩写。表S4：以肺腺癌（LUAD）为暴露因素、蛋白质组为结局的Steiger过滤及反向孟德尔随机化分析结果。注：MR即孟德尔随机化；LUAD即肺腺癌；SNP即单核苷酸多态性；nSNPs为单核苷酸多态性数量；se为标准误；OR为比值比；CI为置信区间；IVW为逆方差加权（inversevariance-weighted）的缩写。表S5：针对9种潜在因果蛋白的贝叶斯共定位分析。可药用基因分为3个层级：第1层级为已获批药物及临床研发阶段药物的靶点；第2层级为与药物靶点密切相关或拥有类药化合物的蛋白；第3层级为细胞外蛋白及关键药物靶点家族成员。注：SNP即单核苷酸多态性（single nucleotide polymorphism）。表S6：已报道的3种潜在因果蛋白的遗传工具相关单核苷酸多态性的全基因组显著关联结果。注：SNP即单核苷酸多态性；chr为染色体；se为标准误；N_samples为样本量；N_cases为病例数；N_controls为对照数。表S7：基于欧洲人群全基因组关联研究（genome-wide association study, GWAS）的危险因素与肺腺癌（LUAD）的孟德尔随机化分析结果。注：MR即孟德尔随机化；LUAD即肺腺癌；GWAS即全基因组关联研究；SNP即单核苷酸多态性；nSNPs为单核苷酸多态性数量；se为标准误；OR为比值比；CI为置信区间；IVW为逆方差加权。表S8：蛋白质组与肺腺癌（LUAD）危险因素的孟德尔随机化分析结果。注：MR即孟德尔随机化；LUAD即肺腺癌；SNP即单核苷酸多态性；nSNPs为单核苷酸多态性数量；se为标准误；OR为比值比；CI为置信区间；IVW为逆方差加权；COPD即慢性阻塞性肺疾病（chronic obstructive pulmonary disease）。表S9：蛋白靶点通过危险因素介导影响肺腺癌（LUAD）的中介分析结果。表S10：通过孟德尔随机化分析筛选得到的与肺腺癌（LUAD）相关的血浆蛋白的可药用性及药物研发概况总结。可药用基因分为3个层级：第1层级为已获批药物及临床研发阶段药物的靶点；第2层级为与药物靶点密切相关或拥有类药化合物的蛋白；第3层级为细胞外蛋白及关键药物靶点家族成员。注：LUAD即肺腺癌；NSCLC即非小细胞肺癌（non-small cell lung cancer）。