Cumulative incidence of diabetes grouped by TCF7L2 SNP genotype. Individuals in the primary (family-based) study (a) who were homozygous for the major allele (C/C genotype, solid line) developed diabetes at a significantly lower rate than patients heterozygous (C/T genotype, dashed line) or homozygous for the minor allele (T/T genotype, dotted line). Results were similar when comparing all three genotypes separately as shown (additive genetic model; p=0.001, logrank) or when grouping genotypes according to dominant (p=0.003) or recessive (p=0.007) genetic models. Modelling of these data indicated that each T allele conferred about a 75% increase in risk of developing diabetes compared with PI CF patients of the same age without a T allele (HR 1.75, 95% CI 1.3–2.4; p=0.0006). The age at which the cumulative incidence reached 25% varied by 7 years with the number of high-risk T alleles (C/C genotype: 27.4 years; C/T genotype: 22.6 years; T/T genotype: 20.0 years). Individuals in the replication (case-control) study (b) who were homozygous for the major allele (C/C genotype, solid line) developed diabetes at a significantly lower rate than patients with one or two copies of the minor allele (C/T genotype, dashed line; or T/T genotype, dotted line). In this study (which had a targeted recruitment strategy based on age and lung function) the data were more consistent with a dominant genetic model, with incidence rates for all three genotypes considered separately being less distinct (p=0.06, logrank), and rates for those with one or two copies of the T allele being significantly greater than for those with none (p=0.02, logrank). Modelling of these data showed association under dominant (HR 1.43, 95% CI 1.1–2.0; p=0.02) or additive (HR 1.3, 95% CI 1.04–1.61, p=0.02) genetic models