Table 2.
Multivariable Logistic Models
| IPF (LTRC) |
IPF (Denver) |
ILA (COPDGene NHW) |
|||||||
|---|---|---|---|---|---|---|---|---|---|
| OR (95% CI) | P Value | AUC | OR (95% CI) | P Value | AUC | OR (95% CI) | P Value | AUC | |
| One genetic predictor per model | |||||||||
| Clinical model* | NA | NA | 0.71 | NA | NA | 0.61 | NA | NA | 0.69 |
| Age | 1.1 (1.02–1.13) | 1.1 × 10−2 | 1.02 (1.01–1.03) | 2.5 × 10−7 | 1.08 (1.06–1.09) | 2.6 × 10−24 | |||
| Sex, male | 3.9 (2.02–7.54) | 4.9 × 10−5 | 1.58 (1.37–1.81) | 2.8 × 10−10 | 0.915 (0.725–1.16) | 4.6 × 10−1 | |||
| Smoking status | NA | NA | 0.63 (0.54–0.73) | 3.0 × 10−9 | NA | NA | |||
| Pack-years of smoking | 1 (0.983–1.02) | 9.6 × 10−1 | NA | NA | 1.01 (1–1.01) | 3.1 × 10−3 | |||
| PRS alone | 3.65 (2.83–4.7) | 1.7 × 10−23 | 0.79 | 2.63 (2.39–2.88) | 9.0 × 10−90 | 0.70 | 1.30 (1.16–1.46) | 6.1 × 10−6 | 0.57 |
| rs35705950-T alone | 3.43 (2.42–4.87) | 5.5 × 10−12 | 0.68 | 4.93 (4.33–5.61) | 3.6 × 10−127 | 0.73 | 1.79 (1.43–2.25) | 5.3 × 10−7 | 0.58 |
| PRS + clinical model | 3.55 (2.7–4.66) | 7.5 × 10−20 | 0.81 | 2.79 (2.52–3.09) | 2.5 × 10−87 | 0.73 | 1.32 (1.18–1.48) | 2.5 × 10−6 | 0.7 |
| rs35705950-T + clinical model | 3.55 (2.43–5.19) | 6.4 × 10−11 | 0.74 | 5.08 (4.43–5.83) | 1.8 × 10−118 | 0.76 | 1.88 (1.48–2.38) | 1.6 × 10−7 | 0.71 |
| Both genetic predictors in a single model with clinical variables | |||||||||
| PRS | 3.49 (2.63–4.64) | 4.9 × 10−18 | 0.84 | 2.74 (2.46–3.05) | 2.4 × 10−75 | 0.81 | 1.31 (1.16–1.47) | 7.4 × 10−6 | 0.72 |
| rs35705950-T | 3.49 (2.26–5.41) | 2.0 × 10−8 | 5.04 (4.34–5.84) | 1.1 × 10−101 | 1.84 (1.45–2.33) | 4.6 × 10−7 | |||
Definition of abbreviations: AUC = area under the receiver operating characteristic curve; CI = confidence interval; COPD = chronic obstructive pulmonary disease; COPDGene = Genetic Epidemiology of COPD; ILA = interstitial lung abnormalities; IPF = idiopathic pulmonary fibrosis; LTRC = Lung Tissue Research Consortium; NA = not applicable; NHW = non-Hispanic white; OR = odds ratio; PRS = polygenic risk score; SPIROMICS = Subpopulations and Intermediate Outcome Measures in COPD Study.
Multivariable logistic models were constructed to test the association of the PRS and the MUC5B rs35705950-T promoter variant with IPF in LTRC and Denver testing cohorts and ILAs in COPDGene NHW. The clinical model included age, sex, and pack-years of smoking or smoking status (as available in each cohort). Models with genetic predictors were adjusted for principal components of genetic ancestry.
Clinical variables are from testing cohorts and are likely overfit.