The association at the RIN3 locus, while genome-wide significant in the overall analysis, was not significant in ICGN. This finding thus may represent a false positive, but it also may be due to the lower power of the family-based analysis. In support of the latter explanation, an alternative analysis using generalized estimating equations (which allows calculation of effect sizes) resulted in an odds ratio of 1•14 (95% confidence interval, 0•92-1•41), consistent with the estimates from our other cohorts. In addition, a lookup of a SNP in strong LD (rs17184313, r2 = 0•94 in EUR) in a recently published meta-analysis of COPD identified from population-based studies22 demonstrates nominal evidence of significance (P = 0•009), though the direction of association was not given. RIN3 is a Rab5 GTPase binding protein expressed in many tissues, including the lung, and is involved in transport 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,
