Table 3.

Multivariable Models Including Clinical Factors, PRS, and TRS for Moderate-to-Severe COPD and Change in FEV₁

Variable	COPDGene Testing Sample				ECLIPSE
	Moderate to Severe COPD		Change in FEV1 (ml/yr)		Change in FEV1 (ml/yr)
	OR (95% CI)	P Value	β (95% CI)	P Value	β (95% CI)	P Value
PRS	1.67 (1.31 to 2.13)	<0.0001	−4.2 (−14 to 5.1)	0.37	1.3 (−5.3 to 8)	0.69
TRS	3.27 (2.38 to 4.5)	<0.0001	−17 (−28 to −6.6)	0.002	−8.2 (−15 to −1)	0.025
Baseline FEV1, L	N/A	N/A	−24 (−38 to −9.9)	0.0011	−34 (−50 to −19)	1.90 × 10−5

Definition of abbreviations: CI = confidence interval; COPD = chronic obstructive pulmonary disease; COPDGene = Genetic Epidemiology of COPD; ECLIPSE = Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points; N/A = not applicable; OR = odds ratio; PRS = polygenic risk score; TRS = transcriptional risk score.

Multivariable models including clinical factors (age, sex, race, pack-years of smoking, current smoking status, and baseline FEV₁ [for change in FEV₁]), PRS, and TRS for moderate to severe COPD and change in FEV₁ (ml/yr) were constructed in the testing sample of COPDGene and replicated in ECLIPSE. Models were also adjusted for principal components of genetic ancestry. Bonferroni-adjusted significance level is 0.05/3 (2 outcomes in COPDGene, 1 outcome in ECLIPSE) = 0.017. The COPDGene testing data set included 624 individuals, of whom 209 had 5-year follow-up spirometric data. ECLIPSE included 468 individuals with microarray and follow-up FEV₁ data; all of these participants had moderate to severe COPD, so replication of this outcome could not be performed.