We hypothesized that multiple genetic variants of the surfactant protein genes, SFTPA1, SFTPA2, SFTPB, SFTPC, and/or SFTPD, are associated with CF or disease severity subgroups (mild and moderate/severe) through single genetic variations within a gene, and through intragenic or intergenic interactions between variants of a single gene or variants of two different genes. Here, SFTPD is linked to cystic fibrosis.