Human molecular genetics
Alternate Journal
Hum. Mol. Genet.

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 

Qiao D, Ameli A, Prokopenko D, Chen H, Kho AT, Parker MM, Morrow J, Hobbs BD, Liu Y, Beaty TH, Crapo JD, Barnes KC, Nickerson DA, Bamshad M, Hersh CP, Lomas DA, Agusti A, Make BJ, Calverley PMA, Donner CF, Wouters EF, Vestbo J, Paré PD, Levy RD, Rennard SI, Tal-Singer R, Spitz MR, Sharma A, Ruczinski I, Lange C, Silverman EK, Cho MH. Whole exome sequencing analysis in severe chronic obstructive pulmonary disease. Human molecular genetics. 2018;27(21):3801-3812. doi:10.1093/hmg/ddy269.