Whole Genome Sequencing in Moderate and Severe Chronic Obstructive Pulmonary Disease

Rationale: Genome-wide association studies have identified multiple common variants associated with chronic obstructive pulmonary disease (COPD). Whole-genome sequencing (WGS) offers comprehensive coverage of the genome, which gives several advantages over exome sequencing and imputation, including improvements in calling of coding regions and interrogation of impactful variants in non-coding regions. We hypothesize that novel variants in non-coding regions, identified through WGS, play an additional role in determining COPD susceptibility. Methods: As part of the NHLBI Trans&# 8208; Omics for Precision Medicine (TOPMed) freeze 5 release, we submitted DNA samples from the COPDGene and Boston Early-Onset COPD studies for sequencing from 2517 non-Hispanic white (NHW) and 723 African American (AA) cases with moderate to very severe COPD (mean forced expiratory volume in 1 …