Authors
Dandi Qiao, Asher Ameli, Dmitry Prokopenko, Han Chen, Alvin T Kho, Margaret M Parker, Jarrett Morrow, Brian D Hobbs, Yanhong Liu, Terri H Beaty, James D Crapo, Kathleen C Barnes, Deborah A Nickerson, Michael Bamshad, Craig P Hersh, David A Lomas, Alvar Agusti, Barry J Make, Peter MA Calverley, Claudio F Donner, Emiel F Wouters, Jørgen Vestbo, Peter D Paré, Robert D Levy, Stephen I Rennard, Ruth Tal-Singer, Margaret R Spitz, Amitabh Sharma, Ingo Ruczinski, Christoph Lange, Edwin K Silverman, Michael H Cho
Publication date
2018/7/27
Journal
Human molecular genetics
Volume
27
Issue
21
Pages
3801-3812
Publisher
Oxford University Press
Description
Chronic obstructive pulmonary disease (COPD), one of the leading causes of death worldwide, is substantially influenced by genetic factors. Alpha-1 antitrypsin deficiency demonstrates that rare coding variants of large effect can influence COPD susceptibility. To identify additional rare coding variants in patients with severe COPD, we conducted whole exome sequencing analysis in 2543 subjects from two family-based studies (Boston Early-Onset COPD Study and International COPD Genetics Network) and one case–control study (COPDGene). Applying a gene-based segregation test in the family-based data, we identified significant segregation of rare loss of function variants in TBC1D10A and RFPL1 (P-value < 2x10–6), but were unable to find similar variants in the case–control study. In single-variant, gene-based and pathway association analyses, we were unable to find significant findings that …
Scholar articles
D Qiao, A Ameli, D Prokopenko, H Chen, AT Kho… - Human molecular genetics, 2018