COPDGene is a study initiative to uncover genetic factors influencing COPD development and classify COPD into subtypes sharing common characteristics. The study involved 10,718 participants aged 45-80 from 21 clinical centres, including 10,263 smokers and 455 non-smoker controls. Multiple genes, including HHIP, FAM13A, AGER, and others, have been identified as high-confidence COPD susceptibility genes through GWAS studies. These genes don't fit previous COPD understanding, and they typically have small effect sizes, suggesting they work together in biological networks. The study identified 82 genome-wide significant loci for COPD. PRS was associated with COPD risk in both European and non-European populations. Combining PRS with clinical factors improved COPD prediction compared to clinical factors alone. PRS also correlated with CT imaging phenotypes, including emphysema patterns and lung growth. Individuals without spirometric COPD but with CT-detected emphysema or gas trapping may experience significant symptoms and exacerbations. Some individuals without airflow obstruction had symptoms similar to COPD patients. PR/Sm was linked to an increased risk of progressing to COPD and an increased risk of death, particularly from cardiovascular disease. Participants with mucus plugs in multiple lung segments were more likely to be older, female, and non-Hispanic White, with a history of smoking, chronic bronchitis, and asthma. They had worse lung function, thicker airway walls, and more emphysema. Mucus plugs were associated with more frequent exacerbations and an increased risk of death, often coinciding with chronic bronchitis, necessitating CT scans for identification. In conclusion, COPDGene's research has shed light on the genetic underpinnings of COPD, the significance of polygenic risk scores, and the impact of mucus plugs on the disease's progression and severity, providing valuable insights into COPD pathogenesis and risk factors.