Case-control study design for lung cancer genetic association studies. (A) subphenotyping for COPD in lung cancer study.30–32 Current and former smokers with >15 pack-year smoking history and spirometry performed to allow subphenotyping in order to establish associations better. (B) COPD status of cases and controls unknown – GWAS approach.23,28,29 Current and former smokers with variable smoking exposure and unknown COPD status could result in spurious associations (confounding/modifying effect) or no association (dilution effect).
Abbreviations: COPD, chronic obstructive pulmonary disease; GWAS, genome-wide association study.