Table 2.
Susceptibility loci for chronic obstructive pulmonary disease (COPD) and related phenotypes identified by genome-wide association studies
| Reference | Study* | Sample size (cases/controls) | Disease/trait | Platform (# SNPs) | Region (size) | Gene | Key SNPs |
|---|---|---|---|---|---|---|---|
| Pillai et al15 | Norway | 823/810 | COPD | Illumina (Human Hap550) | 15q25 | CHRNA3 | rs8034191 |
| ICGN | 1891 | CHRNA5 | rs1051730 | ||||
| NETT-NAS | 389/472 | ||||||
| EOCOPD | 949 | ||||||
| 4q31 | HHIP | rs1828591 | |||||
| rs13118928 | |||||||
| Cho et al19 | Norway | 2940/1380 | COPD | Illumina (Human Hap550 or Quad610) | 4q22 | FAM13A | rs7671167 |
| NETT-NAS | rs1903003 | ||||||
| ECLIPSE | |||||||
| COPDGene | 502/504 | ||||||
| EOCOPD | 949 | ||||||
| ICGN | 2859 | ||||||
| 15q25 | CHRNA3 | rs1062980 | |||||
| CHRNA5 | |||||||
| IREB2 | |||||||
| 4q31 | HHIP | rs1828591 | |||||
| Cho et al20 | ECLIPSE | 1764/178 | COPD | Illumina (Human Hap550, Quad610, or Omni1 Quad) | 19q13 | RAB4B | rs7937 |
| NAS-NETT | 373/435 | EGLN2 | rs2604894 | ||||
| GenKOLS | 863/808 | MIA | |||||
| COPDGene | 499/501 | CYP2A6 | |||||
| ICGN | 983 probands/ 1876 siblings | ||||||
| 4q22 | FAM13A | rs1964516 | |||||
| rs7671167 | |||||||
| 4q31 | HHIP | rs13141641 | |||||
| rs13118928 | |||||||
| 15q25 | CHRNA3 | rs11858836 | |||||
| CHRNA5 | rs13180 | ||||||
| IREB2 | |||||||
| Wilk et al37 | FHS | 1059–1222 | Ten spirometry phenotypes | Affymetrix (70,987) | 10q25 | GSTO2 | rs156697 |
| Wilk et al38 | FHS | 7691 | FEV1/FVC | Affymetrix (500 K + 50 K) | 4q31 | HHIP | rs13147758 |
| Family heart study | 835 | ||||||
| Repapi et al40 | SpiroMeta Consortium | 20,288 | FEV1 and FEV1/FVC | Affymetrix and Illumina (2.5 million) | 4q31 | HHIP | rs12504628 |
| CHARGE consortium | 32,184 | ||||||
| 21,209 | |||||||
| Health 2000 survey | 883 | ||||||
| FEV1 | 2q35 | TNS1 | rs2571445 | ||||
| 4q24 | GSTCD | rs10516526 | |||||
| 5q33 | HTR4 | rs3995090 | |||||
| FEV1/FVC | 6p21 | AGER | rs2070600 | ||||
| 15q23 | THSD4 | rs12899618 | |||||
| Hancock et al39 | CHARGE Consortium | 20,890 | FEV1/FVC | Affymetrix and Illumina (2,515,866) | 2q36 | PID1 | rs1435867 |
| SpiroMeta consortium | 16,178 | ||||||
| 4q22 | FAM13A | rs2869967 | |||||
| 4q31 | HHIP | rs1980057 | |||||
| 5q33 | HTR4 | rs11168048 | |||||
| 5q33 | ADAM19 | rs2277027 | |||||
| 6p21 | AGER-PPT2 | rs2070600 | |||||
| 6q24 | GPR126 | rs3817928 | |||||
| 9q22 | PTCH1 | rs16909898 | |||||
| FEV1 | 4q24 | INTS12 | rs17331332 | ||||
| GSTCD | |||||||
| NPNT | |||||||
| Soler Artigas et al41,** | 23 studies | 48,201 | FEV1 | Illumina and Affymetrix (2,706,349) | 3q26 | MECOM | rs134555 |
| 17 studies | 46,411 | ||||||
| 6p22 | ZKSCAN3 | rs6903823 | |||||
| 10q22 | C10orf11 | rs11001819 | |||||
| FEV1/FVC | 1p36 | MFAP2 | rs2284746 | ||||
| 1q41 | TGFB2- LYPLAL1 | rs993925 | |||||
| 2q37 | HDAC4- FLJ43879 | rs12477314 | |||||
| 3p24 | RARB | rs1529672 | |||||
| 5q15 | SPATA9- RHOBTB3 | rs153916 | |||||
| 6q21 | ARMC2 | rs2798641 | |||||
| 6p21 | NCR3-AIF1 | rs2857595 | |||||
| 12q13 | LRP1 | rs11172113 | |||||
| 12q22 | CCDC38 | rs1036429 | |||||
| 16q13 | MMP15 | rs12447804 | |||||
| 16q23 | CFDP1 | rs2865531 | |||||
| 21q22 | KCNE2- LINC00310 | rs9978142 | |||||
| FEV1 and FEV1/FVC | 10p23 | CDC123 | rs7068966 | ||||
| Imboden et al42 | SAPALDIA | 2677 nonasthmatic, 1441 asthmatic | FEV1 decline in nonasthmatic | Illumina | 13q14 | DLEU7 | rs9316500 |
| ECRHS | Human | ||||||
| EGEA | 610quad | ||||||
| FHS | 10,858 nonasthmatic, 1138 asthmatic | ||||||
| ARIC | |||||||
| B58C | |||||||
| Dutch asthma study | |||||||
| FEV1/FVC decline in asthmatic | 8p22 | TUSC3 | rs4831760 | ||||
| Kong et al43 | ECLIPSE | 1557 | Emphysema (qualitative) | Illumina | 12q11 | BICD1 | rs10844154 |
| Norway | 432 | Human | rs161976 | ||||
| Hap550 (499,578) | |||||||
| Wan et al44 | ECLIPSE | 1734 | Cachexia-related phenotypes (BMI and fat-free mass index) | Illumina | 16q12 | FTO | rs8050136 |
| Norway | 851 | ||||||
| NETT | 365 | ||||||
| COPDGene | 502 |
Notes:
Bold entries indicates replication cohorts;
only the new loci are identified for this study, but ten loci previously reported by Hancock et al39 and Repapi et al40 were also detected.
Abbreviations: ARIC, Atherosclerosis Risk in Communities; B58C, British 1958 Birth Cohort; EOCOPD, Boston Early-Onset COPD Study; BMI, body mass index; COPDGene, COPDGene study; ECLIPSE, Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints; ECRHS, European Community Respiratory Health Survey; EGEA, Epidemiological study on the Genetics and Environment of Asthma; FEV1, forced expiratory volume in 1 second; FHS, Framingham Heart Study; FVC, forced vital capacity; GenKOLS, Bergen, Norway COPD Cohort; ICGN, International COPD Genetics Network study; NAS-NETT, Normative Aging Study and National Emphysema Treatment Trial; SAPALDIA, Swiss Cohort Study on Air Pollution and Lung and Heart Disease in Adults; SNPs, single-nucleotide polymorphisms.