Genetic loci associated with chronic obstructive pulmonary disease overlap with loci for lung function and pulmonary fibrosis

Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide1. We performed a genetic association in 15,256 cases and 47,936 controls, with replication of select top results (P < 5x10-6) in 9,498 cases and 9,748 controls. In the combined meta-analysis, we identified 22 loci at genome-wide significance, including 13 new associations with COPD. Nine of these 13 loci have been associated with lung function in general population samples2-7; however, 4 (EEFSEC, DSP, MTCL1, and SFTPD) are novel. We noted 2 loci shared with pulmonary fibrosis8,9 (FAM13A and DSP) but with opposite risk alleles for COPD. None of our loci overlapped with genome-wide associations for asthma; however, one locus has been implicated in the joint susceptibility to asthma and obesity10. We also identified genetic correlation between COPD and asthma. Our findings highlight novel loci, demonstrate the importance of specific lung function loci to COPD, and identify potential regions of genetic overlap between COPD and other respiratory diseases

Genome-wide association analysis identifies six new loci associated with forced vital capacity

Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10(-8)) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease