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Background  Vitamin D is associated with lung function in cross-sectional studies, and vitamin D inadequacy is hypothesized to play a role in the pathogenesis of chronic obstructive pulmonary disease. Further data are needed to clarify the relation between vitamin D status, genetic variation in vitamin D metabolic genes, and cross-sectional and longitudinal changes in lung function in healthy adults.    Methods  We estimated the association between serum 25-hydroxyvitamin D [25(OH)D] and cross-sectional forced expiratory volume in the first second (FEV 1 ) in Framingham Heart Study (FHS) Offspring and Third Generation participants and the association between serum 25(OH)D and longitudinal change in FEV 1  in Third Generation participants using linear mixed-effects models. Using a gene-based approach, we investigated the association between 241 SNPs in 6 select vitamin D metabolic genes in relation to longitudinal change in FEV 1  in Offspring participants and pursued replication of these findings in a meta-analyzed set of 4 independent cohorts.    Results  We found a positive cross-sectional association between 25(OH)D and FEV 1  in FHS Offspring and Third Generation participants ( P  = 0.004). There was little or no association between 25(OH)D and longitudinal change in FEV 1  in Third Generation participants ( P  = 0.97). In Offspring participants, the  CYP2R1  gene, hypothesized to influence usual serum 25(OH)D status, was associated with longitudinal change in FEV 1  (gene-based  P  < 0.05). The most significantly associated SNP from  CYP2R1  had a consistent direction of association with FEV 1  in the meta-analyzed set of replication cohorts, but the association did not reach statistical significance thresholds ( P  = 0.09).    Conclusions  Serum 25(OH)D status was associated with cross-sectional FEV 1 , but not longitudinal change in FEV 1 . The inconsistent associations may be driven by differences in the groups studied.  CYP2R1  demonstrated a gene-based association with longitudinal change in FEV 1  and is a promising candidate gene for further studies.    Electronic supplementary material  The online version of this article (doi:10.1186/s12931-015-0238-y) contains supplementary material, which is available to authorized users.

Association of 25-Hydroxyvitamin D status and genetic variation in the vitamin D metabolic pathway with FEV1 in the Framingham Heart Study