Subjects from the International COPD Genetics Network (ICGN) were used as the primary replication population. In the multi-center ICGN study [22],[23] subjects with known COPD were recruited as probands, and siblings and available parents were ascertained through the probands. Inclusion criteria for probands were post-bronchodilator FEV1<60% predicted and FEV1/VC <90% predicted at a relatively early age (45 to 65 years), a≥5 pack-year smoking history, and at least one eligible sibling with a≥5 pack-year smoking history. COPD in siblings was defined by a post-bronchodilator FEV1<80% predicted and FEV1/VC<90% predicted. The same exclusion criteria used in the Bergen study were also applied for the ICGN population. In total, 1891 Caucasian individuals from 606 pedigrees were included in the ICGN family-based association analysis.
