Table 4. . Associations with gene expression (unadjusted p < 0.05) in the Asan Biobank for genes to which differentially methylated probes or genes annotated, ordered by chromosomal location.
| Chr† | Trait | Differentially methylated probes in relation to lung function (the Korean COPD cohort) | Gene | Differentially expressed genes in relation to lung function in lung tissue (Asan Biobank) | |||||
|---|---|---|---|---|---|---|---|---|---|
| Differentially methylated probe | |||||||||
| Probe or region‡ | Coef | p-value§ | Genomic feature | Transcript | Coef | p-value | |||
| 10 | Ratio | cg03559389 | -6.9 | 8.1 × 10-8 | Body | DIP2C | NM_014974 | -0.029 | 6.5 × 10-5 |
| 11 | cg06022671 | -2.6 | 3.7 × 10-6 | PATL1 | NM_152716 | -0.015 | 1.3 × 10-6 | ||
| Differentially methylated region | |||||||||
| Start–end (bp) | #CpGs | FDR¶ | |||||||
| 1 | Ratio | 55353149-55353706 | 5 (4) | 0.002 | TSS1500; promoter | DHCR24 | NM_014762 | -3.9 × 10-4 | 0.005 |
| COPD# | 110752952-110754257 | 10 (6) | 1.9 × 10-4 | TSS1500; TSS200; 1stExon; promoter | KCNC4 | NM_001039574 | -0.424 | 0.036 | |
| 2 | COPD | 74347215-74347776 | 4 (3) | 0.010 | BOLA3 (-15313) | NM_001035505 | 0.110 | 5.3 × 10-5 | |
| Ratio | 102313644-102314757 | 8 (2) | 0.004 | TSS1500; TSS200; 1stExon; body; promoter (cell type specific) | MAP4K4 | NM_145686 | -0.006 | 7.5 × 10-5 | |
| Ratio | 113992762-113993313 | 8 (8) | 1.8 × 10-5 | Body; promoter (cell type specific); DHS | PAX8 | NM_013952 | 0.048 | 1.7 × 10-4 | |
| COPD | 220083306-220083951 | 10 (5) | 0.006 | 1stExon; 5′UTR; TSS200; TSS1500; promoter | ABCB6 | NM_005689 | 0.578 | 8.9 × 10-4 | |
| 3 | COPD | 167452484-167453518 | 13 (3) | 5.4 × 10-5 | 5′UTR; TSS200; TSS1500; promoter; DHS | PDCD10 | NM_007217 | -0.097 | 0.002 |
| 4 | COPD | 20253130-20254519 | 8 (7) | 1.9 × 10-4 | TSS1500 | SLIT2 | NM_004787 | -0.087 | 5.0 × 10-5 |
| 5 | COPD | 140800398-140800929 | 8 (4) | 8.6 × 10-4 | Body; DHS | PCDHGA4 | NM_032053 | -2.093 | 1.6 × 10-4 |
| 7 | COPD | 27182637-27185512 | 48 (26) | 3.5 × 10-14 | Body; 1stExon; 5′UTR; TSS200; TSS1500; 3′UTR; body; DHS | HOXA5 | NM_019102 | 0.049 | 0.021 |
| 8 | Ratio | 98610507-98610888 | 3 (3) | 0.007 | MTDH (-45900) | NM_178812 | -0.006 | 0.002 | |
| Ratio | 99960843-99961768 | 6 (4) | 0.005 | 5′UTR; body; enhancer | OSR2 | NM_053001 | -0.012 | 0.036 | |
| COPD | 144358043-144359316 | 5 (5) | 3.1 × 10-4 | Body; 3′UTR; promoter | GLI4 (9709) | NM_138465 | 0.761 | 1.2 × 10-5 | |
| COPD | 144659627-144661051 | 11 (8) | 0.003 | Body; TSS200; TSS1500; promoter | NAPRT1 | NM_145201 | 0.135 | 0.005 | |
| 10 | COPD | 105212236-105213309 | 11 (5) | 1.5 × 10-4 | TSS200; TSS1500; 3′UTR; enhancer; Promoter | CALHM2 | NM_015916 | 0.173 | 0.003 |
| 11 | Ratio | 94277826-94279068 | 11 (5) | 0.002 | 1stExon; enhancer; Promoter (cell type specific) | FUT4 | NM_002033 | -0.043 | 0.004 |
| COPD | 108408907-108409825 | 7 (5) | 5.8 × 10-4 | Body; TSS1500 | EXPH5 | NM_015065 | -0.385 | 0.002 | |
| 12 | COPD | 2943902-2944493 | 6 (6) | 2.9 × 10-4 | 1stExon; 5′UTR; TSS200; TSS1500; Enhancer; DHS | NRIP2 | NM_031474 | -0.840 | 0.004 |
| 16 | COPD | 67232921-67233983 | 6 (4) | 2.2 × 10-4 | TSS200; 1stExon; body; enhancer; DHS | ELMO3 | NM_024712 | 0.535 | 2.1 × 10-6 |
| COPD | 88772396-88772985 | 6 (4) | 0.005 | TSS1500; 1stExon; promoter | CTU2 | NM_001012759 | 0.877 | 1.8 × 10-5 | |
| Ratio | 6 (5) | 0.002 | 0.026 | 5.2 × 10-5 | |||||
| 17 | COPD | 33759484-33760527 | 12 (10) | 3.1 × 10-4 | 1stExon; TSS200; TSS1500; DHS | SLFN12 | NM_018042 | -0.539 | 1.6 × 10-4 |
| COPD | 73824354-73825227 | 6 (4) | 0.003 | Body; enhancer; promoter | UNC13D | NM_199242 | 0.072 | 0.010 | |
| COPD | 76797750-76798776 | 6 (4) | 0.008 | Body | USP36 | NM_025090 | -0.262 | 3.5 × 10-5 | |
| Ratio | 6 (3) | 0.002 | -0.006 | 8.7 × 10-4 | |||||
| 18 | Ratio | 74114570-74114728 | 3 (3) | 4.8 × 10-4 | Body | ZNF516 | NM_014643 | -0.042 | 2.7 × 10-7 |
| COPD | 3 (3) | 0.003 | -1.276 | 1.1 × 10-6 | |||||
| 19 | COPD | 11517079-11517436 | 4 (4) | 0.003 | Body | RGL3 | NM_001161616 | 0.084 | 0.003 |
| Ratio | 37958346-37959104 | 8 (4) | 7.2 × 10-4 | TSS200; TSS1500; promoter | ZNF570 | NM_144694 | -0.032 | 0.008 | |
| FEV1†† | 51520093-51520658 | 6 (3) | 1.5 × 10-4 | Body; DHS | KLK10 | NM_002776 | 1.381 | 0.010 | |
| Ratio | 6 (4) | 3.0 × 10-4 | 0.008 | 0.015 | |||||
| 21 | COPD | 38362230-38363160 | 8 (6) | 0.003 | 5′UTR; TSS200; TSS1500; promoter | HLCS | NM_001242785 | -1.268 | 6.7 × 10-7 |
| 22 | COPD | 51016501-51017432 | 15 (9) | 5.3 × 10-5 | 5′UTR; TSS200; 1stExon; TSS1500; Enhancer; DHS | CPT1B | NM_001145135 | 0.197 | 0.001 |
| FEV1 | 51016501-51017723 | 16 (12) | 1.0 × 10-14 | 0.820 | 0.027 | ||||
†Chromosome.
‡Start-end position of each region (bp).
§Statistical significance from statistical model.
¶False discovery rate from DMRcate.
#Chronic obstructive pulmonary disease.
††Forced expiratory volume in one second.
Genomic features were based on Illumina's Annotation file and those for DMRs were based on CpGs at start and end position of each region. Categories for the features includes (1) body, gene body; (2) 5′UTR, 5 prime untranslated region; (3) 3′UTR, 3 prime untranslated region; (4) TSS200, 200 basepair within transcription start site; (5) TSS1500, 1500 basepair within transcription start site; and (6) DHS, DNase I hypersensitivity site.
Differentially methylated probes or regions in this Table were located inside each mapped gene.
COPD: Chronic obstructive pulmonary disease; DHS: DNaseI hypersensitivity site; FEV: Forced expiratory volume in 1 second; FVC: Forced vital capacity.