Performance characteristics of ICD-10 code and algorithms.

Performance characteristics of ICD-10 code and algorithms.</p

Select comparisons of patients identified by Algorithm 2 compared to patients with ICD-10 code use at least two times.

Select comparisons of patients identified by Algorithm 2 compared to patients with ICD-10 code use at least two times.</p

Cohort assembly.

Overview of multi-stage process for SSc ICD-10 code validation and algorithm testing and validation. Patients were selected from healthsystem databases if the ICD-10 code was present at least twice in encounters, billing codes or the problem list. Of the 2138 potential patients 1183 were excluded and a random selection of 100 patients underwent code validation. The 955 patient cohort was divided in half for testing of two algorithms using disease manifestation keywords and internal validation of highest performing algorithm. When applied to the entire cohort, 788 patients were identified as likely cases. ICD-10 = International Classification of Diseases, Tenth Revision.</p

Characteristics of patients based on case classification N = 100 (baseline validation cohort).

Characteristics of patients based on case classification N = 100 (baseline validation cohort).</p

Characteristics of entire cohort by randomization for baseline code validation subset n = 955.

Characteristics of entire cohort by randomization for baseline code validation subset n = 955.</p

Additional file 1 of Bronchial epithelial gene expression and interstitial lung abnormalities

Additional file 1: Table S1. Institutional Review Board committee names and project approval numbers for each center for the DECAMP Study

Overlap of genetic risk between interstitial lung abnormalities and idiopathic pulmonary fibrosis

Rationale Interstitial lung abnormalities (ILA) are associated with the highest genetic risk locus for IPF; however, the extent to which there is additional overlap with IPF, or unique associations among those with ILA is not known. Objectives To perform a genome-wide association study (GWAS) of ILA. Methods: ILA and the subpleural-predominant subtype were assessed on chest computed tomography (CT) scans in the AGES, COPDGene, Framingham Heart, ECLIPSE, MESA, and SPIROMICS studies. We performed a GWAS of ILA in each cohort and combined the results using a meta-analysis. We assessed for overlapping associations in independent GWASs of IPF. Measurements and Main Results Genome-wide genotyping data were available in 1,699 ILA cases and 10,274 controls. The MUC5B promoter variant rs35705950 was significantly associated with both ILA (p=2.6x10-27) and subpleural ILA (p=1.6x10-29). We discovered novel genome-wide associations near IPO11 (rs6886640, p=3.8x10-8 ) and FCF1P3 (rs73199442, p=4.8x10-8 ) with ILA, and HTRE1 (rs7744971, p=4.2x10-8 ) with subpleural-predominant ILA. These novel associations were not associated with IPF. Of 12 previously reported IPF GWAS loci, 5 (DPP9, DSP, FAM13A, IVD, and MUC5B) were significantly associated (p<0.05/12) with ILA. Conclusions In a GWAS of ILA in six studies, we confirmed the association with a MUC5B promoter variant and found strong evidence for an effect of previously described IPF loci; however, novel ILA associations were not associated with IPF. These findings highlight common and suggest distinct genetically-driven biologic pathways between ILA and IPF