Whole genome sequence analysis of pulmonary function and COPD in 19,996 multi-ethnic participants.
Chronic obstructive pulmonary disease (COPD), diagnosed by reduced lung function, is a leading cause of morbidity and mortality. We performed whole genome sequence (WGS) analysis of lung function and COPD in a multi-ethnic sample of 11,497 participants from population- and family-based studies, and 8499 individuals from COPD-enriched studies in the NHLBI Trans-Omics for Precision Medicine (TOPMed) Program. We identify at genome-wide significance 10 known GWAS loci and 22 distinct, previously unreported loci, including two common variant signals from stratified analysis of African Americans. Four novel common variants within the regions of PIAS1, RGN (two variants) and FTO show evidence of replication in the UK Biobank (European ancestry n ~ 320,000), while colocalization analyses leveraging multi-omic data from GTEx and TOPMed identify potential molecular mechanisms underlying four of the 22 novel loci. Our study demonstrates the value of performing WGS analyses and multi-omic follow-up in cohorts of diverse ancestry.
Duke Scholars
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- Whole Genome Sequencing
- Small Ubiquitin-Related Modifier Proteins
- Respiratory Physiological Phenomena
- Pulmonary Disease, Chronic Obstructive
- Protein Inhibitors of Activated STAT
- Polymorphism, Single Nucleotide
- Middle Aged
- Male
- Lung
- Intracellular Signaling Peptides and Proteins
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Whole Genome Sequencing
- Small Ubiquitin-Related Modifier Proteins
- Respiratory Physiological Phenomena
- Pulmonary Disease, Chronic Obstructive
- Protein Inhibitors of Activated STAT
- Polymorphism, Single Nucleotide
- Middle Aged
- Male
- Lung
- Intracellular Signaling Peptides and Proteins