Supplementary information Figure S1 Correlation of infiltrating eosinophils and total IgE in nasal tissues of patients with CRSwNP. The percentage of infiltrating eosinophils and concentrations of total IgE were assessed in nasal tissues of CRSwNP (n=17) and correlations were analyzed by Spearman correlation. CRSwNP: chronic rhinosinusitis with nasal polyps. Figure S2: Differentially expressed mRNAs (DE-mRNAs) and differentially expressed lncRNAs (DE-lncRNAs) in nasal tissues of CRSwNP patients. (A-B) Venn diagrams depicting significant DE-mRNAs and DE-lncRNAs identified by RNA sequencing in CRSwNP with comorbid asthma (CRSwNP+AS) (n=10), CRSwNP-alone (n=10), and control (Ctrl) (n=9) subjects. The number of DE-mRNAs or DE-lncRNAs is shown in the corresponding areas. CRSwNP: chronic rhinosinusitis with nasal polyps; AS: asthma; lncRNA: long non-coding RNA; DE: differentially expressed. Figure S3: Hierarchical clustering of differentially expressed genes. Heat map showing top 500 differentially expressed genes. Background factors (gender, smoking, atopy, disease condition) of subjects are marked in the corresponding areas. CRSwNP+AS (n=10), CRSwNP-alone (n=10), and control (n=9). CRSwNP: chronic rhinosinusitis with nasal polyps; AS: asthma. Figure S4 GO biological processes enriched by common dysregulated genes in CRSwNP with comorbid asthma (CRSwNP+AS) and CRSwNP-alone. The result was visualized by cytoscape network. Node size represented gene number in node and node filled color represented P value. CRSwNP: chronic rhinosinusitis with nasal polyps; AS: asthma; GO: gene ontology. Figure S5 Gene number of modules identified by weighted gene co-expression network analysis (WGCNA). WGCNA was applied to explore the potential functions of 176 common DE-lncRNAs, based on a coexpression network of DE-lncRNAs and DE-mRNAs. Branches of the dendrogram obtained by hierarchical clustering of adjacency based similarity result in 9 modules, labelled with distinct colours. Gene number of each module is shown above the corresponding column. lncRNA: long non-coding RNA; DE: differentially expressed. Figure S6 The expression and potential functions of LINC01146. (A) The expression of LINC01146 in CRSwNP with comorbid asthma (CRSwNP+AS), CRSwNP-alone and control group. ** P<0.01. (B) LINC01146 gene locus and adjacent genes. Spearman correlation analysis was performed between expression of LINC01146 and GALC. (C) Top 10 KEGG pathways significantly enriched by coexpressed mRNAs of LINC01146. Values of P<0.05 were considered statistically significant. CRSwNP: chronic rhinosinusitis with nasal polyps; AS: asthma. Figure S7 Gene modules identified by weighted gene co-expression network analysis (WGCNA) based on expression of differentially expressed mRNAs (DE-mRNAs) and differentially expressed lncRNAs (DE-lncRNAs) in CRSwNP with comorbid asthma (CRSwNP+AS) versus CRSwNP-alone. Branches of the dendrogram obtained by hierarchical clustering of adjacency based similarity demonstrated 7 modules, labelled with distinct colours. CRSwNP: chronic rhinosinusitis with nasal polyps; AS: asthma; lncRNA: long non-coding RNA; DE: differentially expressed. Figure S8 Asthma related genes expressed in nasal tissue of CRSwNP patients with comorbid asthma (CRSwNP+AS) and patients with CRSwNP-alone. CRSwNP+AS (n=10), CRSwNP-alone (n=10), and control (n=9). CRSwNP: chronic rhinosinusitis with nasal polyps; AS: asthma; FPKM: Fragments per kilo-base of exon per million fragments mapped. Table S1. Demographic and clinical characteristics of study subjects Control CRSwNP-alone CRSwNP + AS P value Subjects 31 99 65 NA Sex (male/female) 16/15 61/38 36/29 0.427 Age (years±SD) 49.10±13.82 44.65±11.72 45.60±11.27 0.603 Atopy (yes/no) 5/26 22/77 25/40* 0.025 Smoker (yes/no) 7/24 23/76 14/51 0.796 Recurrence (yes/no) NA 21/78 26/39* 0.009 FEV1/FVC%, median (IQR) NA 88.65 (84.14-90.96) 80.19 (68.53-85.41)* <0.001 FENO, median (IQR) NA 17.00 (12.25-23.00) 33.50 (19.00-57.00)* <0.001 Peripheral blood eosinophils (%), 1.70 (1.10-2.30) 3.00 (1.50-4.90) 6.45 (4.08-8.80)* <0.001 median (IQR) Peripheral blood total IgE (kU/l), 14.40 (22.50-60.80) 53.90 (22.37-90.88) 143.00 (73.15-308.0)* <0.001 median (IQR) Tissue eosinophils (%), NA 9.58 (3.18-34.55) 34.78 (26.34-54.45)* 0.002 median (IQR) Tissue neutrophils (%), NA 10.16 (2.75-16.22) 7.21 (1.58-16.34) 0.425 median (IQR) Tissue lymphocytes (%), NA 56.42 (32.49-69.23) 38.79 (19.20-45.06)* 0.037 median (IQR) Tissue plasma cells (%), NA 12.75 (7.95-21.26) 16.54 (12.74-21.81) 0.515 median (IQR) Tissue total IgE(ng/ml), 3.48 (2.03-8.64) 9.47 (4.63-19.98) 90.98 (39.91-137.55)* <0.001 median (IQR) * CRSwNP+AS vs CRSwNP-alone. CRSwNP: chronic rhinosinusitis with nasal polyps; AS: asthma. Table S2. Common DE-mRNAs and DE-lncRNAs shared by CRSwNP-alone versus control and CRSwNP+AS versus control CRSwNP-alone vs. Control CRSwNP+AS vs. Control Gene identifier Gene name Gene type Log2(Fold Log2(Fold P value P value Change) Change) ENSG00000000938 FGR mRNA 1.363 2.991E-07 2.002 1.330E-12 ENSG00000002587 HS3ST1 mRNA 1.320 5.218E-10 1.194 2.934E-07 ENSG00000002726 AOC1 mRNA 2.582 2.067E-05 2.715 1.269E-05 ENSG00000002933 TMEM176A mRNA 1.542 2.176E-13 1.642 1.457E-12 ENSG00000003249 DBNDD1 mRNA -2.091 1.412E-15 -1.830 2.289E-10 ENSG00000004468 CD38 mRNA 1.502 1.786E-07 1.591 1.429E-04 ENSG00000004660 CAMKK1 mRNA -1.914 9.762E-17 -1.172 1.212E-05 ENSG00000004848 ARX mRNA -2.866 1.009E-04 -2.716 3.124E-04 ENSG00000005059 CCDC109B mRNA 1.647 2.449E-12 1.184 6.296E-04 ENSG00000005379 BZRAP1 mRNA -1.948 1.154E-13 -1.047 1.458E-03 ENSG00000005513 SOX8 mRNA -4.699 6.168E-43 -3.084 6.873E-12 ENSG00000005981 ASB4 mRNA -1.866 1.121E-04 -1.500 1.084E-03 ENSG00000006071 ABCC8 mRNA -2.735 2.813E-09 -2.024 4.787E-04 ENSG00000006074 CCL18 mRNA 6.938 2.438E-12 8.880 5.284E-38 ENSG00000006128 TAC1 mRNA -2.891 5.193E-05 -2.233 4.927E-03 ENSG00000006377 DLX6 mRNA -1.314 1.458E-03 -1.520 1.202E-03 ENSG00000006576 PHTF2 mRNA 1.753 1.203E-08 1.244 1.834E-03 ENSG00000006740 ARHGAP44 mRNA -1.439 8.561E-08 -1.676 7.124E-11 ENSG00000007216 SLC13A2 mRNA -4.510 5.905E-46 -3.832 1.854E-16 ENSG00000007314 SCN4A mRNA -2.535 2.775E-12 -2.756 1.508E-09 ENSG00000007516 BAIAP3 mRNA -1.887 2.231E-04 -1.986 5.195E-05 ENSG00000007968 E2F2 mRNA 1.821 2.022E-05 1.966 4.043E-06 ENSG00000008283 CYB561 mRNA -1.678 1.704E-15 -1.630 3.489E-13 ENSG00000008441 NFIX mRNA -1.903 9.730E-24 -1.456 5.071E-08 ENSG00000008516 MMP25 mRNA 1.553 3.733E-05 2.522 2.782E-08 ENSG00000008735 MAPK8IP2 mRNA -2.214 3.098E-13 -1.312 5.158E-04 ENSG00000009694 TENM1 mRNA -1.790 3.207E-04 -2.639 1.646E-06 ENSG00000009790 TRAF3IP3 mRNA 1.452 2.909E-06 1.352 3.834E-05 ENSG00000010610 CD4 mRNA 1.282 3.592E-07 1.740 6.099E-10 ENSG00000011347 SYT7 mRNA -2.528 1.340E-10 -2.657 2.325E-11 ENSG00000011426 ANLN mRNA 2.990 1.226E-14 2.356 3.240E-07 ENSG00000011600 TYROBP mRNA 2.102 3.467E-16 2.386 1.772E-17 ENSG00000012223 LTF mRNA -5.519 4.364E-32 -4.285 1.084E-11 ENSG00000012660 ELOVL5 mRNA 1.381 7.457E-09 1.399 3.331E-06 ENSG00000012779 ALOX5 mRNA 1.197 5.690E-08 1.668 1.484E-10 ENSG00000015285 WAS mRNA 1.317 6.102E-07 1.644 4.939E-08 ENSG00000016391 CHDH mRNA -2.514 2.192E-22 -1.529 6.757E-08 ENSG00000016490 CLCA1 mRNA 4.994 6.521E-03 8.494 1.837E-10 ENSG00000017373 SRCIN1 mRNA -2.694 2.189E-14 -2.286 5.552E-10 ENSG00000018280 SLC11A1 mRNA 1.581 1.296E-03 1.963 2.199E-05 ENSG00000018625 ATP1A2 mRNA -1.712 1.086E-08 -1.218 1.092E-04 ENSG00000019169 MARCO mRNA 3.442 4.480E-09 7.840 3.180E-15 ENSG00000019505 SYT13 mRNA -3.812 1.160E-10 -3.814 8.564E-14 ENSG00000021300 PLEKHB1 mRNA -2.130 4.145E-11 -1.657 4.254E-08 ENSG00000023445 BIRC3 mRNA 1.512 7.837E-06 1.804 3.521E-04 ENSG00000024526 DEPDC1 mRNA 3.470 6.694E-12 2.725 1.083E-04 ENSG00000026103 FAS mRNA 1.794 1.612E-12 1.251 8.038E-04 ENSG00000026508 CD44 mRNA 1.802 2.109E-09 1.758 3.464E-06 ENSG00000026751 SLAMF7 mRNA 1.426 4.517E-05 1.324 9.837E-04 ENSG00000029153 ARNTL2 mRNA 1.924 9.384E-19 1.612 1.602E-08 ENSG00000029559 IBSP mRNA -4.158 5.171E-05 -3.140 4.729E-03 ENSG00000029993 HMGB3 mRNA 1.300 1.302E-08 1.069 1.485E-04 ENSG00000034063 UHRF1 mRNA 1.666 7.620E-05 1.296 1.491E-03 ENSG00000035499 DEPDC1B mRNA 2.913 1.450E-10 2.530 9.649E-07 ENSG00000037749 MFAP3 mRNA 1.336 4.480E-07 1.071 4.651E-03 ENSG00000038427 VCAN mRNA 1.556 3.348E-09 1.184 2.950E-04 ENSG00000038945 MSR1 mRNA 2.761 2.462E-16 2.410 3.161E-12 ENSG00000041515 MYO16 mRNA 3.342 3.981E-13 1.884 2.325E-04 ENSG00000043039 BARX2 mRNA -3.892 3.110E-23 -3.190 9.519E-11 ENSG00000043462 LCP2 mRNA 2.326 1.943E-14 2.292 8.401E-11 ENSG00000043591 ADRB1 mRNA -1.214 9.870E-04 -1.136 6.207E-03 ENSG00000044524 EPHA3 mRNA -1.995 6.260E-07 -1.922 3.654E-05 ENSG00000048028 USP28 mRNA 1.104 6.469E-07 1.206 9.301E-05 ENSG00000048540 LMO3 mRNA -1.489 1.529E-02 -1.868 2.132E-03 ENSG00000048740 CELF2 mRNA 1.256 1.417E-05 1.284 2.157E-04 ENSG00000049089 COL9A2 mRNA -2.404 5.416E-17 -1.485 3.712E-04 ENSG00000049130 KITLG mRNA 1.591 1.341E-09 1.165 8.655E-04 ENSG00000049192 ADAMTS6 mRNA 1.462 1.401E-04 1.364 9.474E-04 ENSG00000049768 FOXP3 mRNA 2.268 1.465E-10 1.568 1.303E-04 ENSG00000051180 RAD51 mRNA 1.630 3.170E-05 1.065 6.428E-03 ENSG00000052344 PRSS8 mRNA -2.359 1.382E-22 -2.084 1.673E-10 ENSG00000054179 ENTPD2 mRNA -1.438 5.814E-06 -1.537 2.124E-07 ENSG00000054277 OPN3 mRNA 1.112 1.749E-05 1.087 7.740E-04 ENSG00000054803 CBLN4 mRNA -1.874 3.646E-03 -2.306 8.354E-04 ENSG00000057149 SERPINB3 mRNA 2.646 1.878E-24 1.609 1.912E-05 ENSG00000057294 PKP2 mRNA -1.728 7.620E-17 -1.559 9.081E-09 ENSG00000058453 CROCC mRNA -2.541 4.145E-08