from plasma membranes to early endosomes69,70. High levels of expression of RIN3 have been found on human mast cells71, a cell type that may be of interest in COPD72–74. Furthermore, we demonstrated, in a small number of lung tissue samples, that RIN3 expression differs between COPD cases versus controls. While RIN3 is the closest gene to the lead SNP, this locus is also approximately 1•7 megabases away from SERPINA1, the gene encoding alpha-1 antitrypsin, which could suggest an effect of distant rare variants75. For the loci reported in this study, and for most loci reported for GWAS, the role of candidate SNP(s) on a particular gene and on protein function cannot be deduced with certainty from linkage disequilibrium patterns and simple measures of gene expression, and requires further functional investigation including SNP-based functional studies76,77.
