We analysed the relationship between genetic ancestry and type 2 diabetes status in two Latino populations from Mexico and Colombia. Both of these populations inherit European, Native American and African ancestry, but we focused our analysis on the proportion of European ancestry as inferred from using 67 AIMs. In the Mexicans, we observed a statistically significant difference (OR [95% CI] 0.06 [0.02–0.21], p=2 × 10−5) in genetic ancestry between patients with type 2 diabetes and age- and sex-matched controls from central Mexico (). A similar phenomenon, although of lesser magnitude, was observed for the Colombians, with a nominally significant difference (OR 0.26 [0.08–0.78], p=0.02) in genetic ancestry between diabetic participants and non-diabetic controls (). This ancestry difference was due to participants with type 2 diabetes having less European ancestry in both groups (). Overall, the proportion of European ancestry is estimated to be 33% in diabetic participants vs 46% in controls in Mexicans, and 56 vs 59% respectively in Colombians.
Histograms of European ancestry proportions in type 2 diabetes participants and controls from Mexico (a) and Colombia (b), using 67 AIMs. Black bars, type 2 diabetes; grey bars, controls
We investigated whether the observed association between genetic ancestry and type 2 diabetes was confounded by socioeconomic status. We determined that socioeconomic status was strongly correlated with European ancestry proportion in Mexicans (33% correlation, p=4 × 10−7) and Colombians (34% correlation, p=2 × 10−19), and therefore could potentially confound associations between genetic ancestry and type 2 diabetes. In the Mexicans, socioeconomic status was strongly predictive of case-control status (p=2 × 10−10) and when socioeconomic status and ancestry were analysed together, the association between non-European ancestry and type 2 diabetes was significantly attenuated (OR 0.17 [0.04–0.71], p=0.02) (). In the Colombians, the association between socioeconomic status and type 2 diabetes was weaker, but still strongly significant due to the larger sample size (p=8 × 10−7). Inclusion of both socioeconomic status and ancestry in the model abolished the significance of the ancestry- phenotype relationship (OR 0.64 [0.19–2.12], p=0.46) (). For both populations, inclusion of socioeconomic status in the model reduced the effect size as well as the statistical significance of the association between ancestry and type 2 diabetes (). However, in each case, the effect size and statistical significance of the association between socioeconomic status and type 2 diabetes was little changed by accounting for ancestry ().
Association of non-European ancestry with type 2 diabetes in Latinos is confounded by socioeconomic status
As an alternative way to investigate the association between non-European ancestry and type 2 diabetes while accounting for socioeconomic status, we conducted a stratified analysis, in which we analysed each socioeconomic status stratum separately. We excluded the eight Colombian samples in socioeconomic status stratum 6 from this analysis, so that five strata were analysed for each population. In Mexicans and Colombians, the association between ancestry and type 2 diabetes did not reach statistical significance (nominal p=0.01, corrected p=0.05 after accounting for five statistical tests) for any stratum (). These results are consistent with the greatly reduced association between ancestry and type 2 diabetes when accounting for socioeconomic status ().
Fig. 2 Distribution of ancestry proportions across strata of socioeconomic status (SES) in (a) Mexicans and (b) Colombians. Distribution of mean socioeconomic status scores across strata of increasing proportion of European ancestry in (c) Mexicans and (d) Colombians. (more ...)
We also conducted a stratified analysis in which we considered each of five ancestry strata (0–20, 20–40, 40–60, 60–80 or 80–100% European ancestry) and analysed associations between socioeconomic status and type 2 diabetes within each stratum (). For Mexicans, we obtained nominal p values of 0.003, 0.12, 0.00001, 0.11 and 0.01, each with a negative coefficient for socioeconomic status. For Colombians, we excluded ancestry stratum 0–20% (which contained only six samples, each with type 2 diabetes) and obtained nominal p values of 0.004, 0.0006, 0.006 and 0.49, with a negative coefficient for socioeconomic status for each of the three significant p values. These results are consistent with the association between socioeconomic status and type 2 diabetes remaining strong after accounting for ancestry ().
We finally considered whether BMI confounds the observed associations between either socioeconomic status or non-European ancestry and type 2 diabetes. We determined that BMI is negatively correlated with socioeconomic status in Mexicans (−20% correlation, p=0.002) and Colombians (−7% correlation, p=0.05), but that correlations between BMI and European ancestry proportion are not statistically significant in Mexicans (−12% correlation, p=0.06) or in Colombians (−1% correlation, p=0.72). The significant negative correlation between BMI and socioeconomic status implies that BMI could potentially confound our analyses. However, inclusion of BMI as a covariate in our analyses did not change the effect size or statistical significance of the associations of socioeconomic status and non-European ancestry with type 2 diabetes either in Mexicans or in Colombians, even though BMI itself was associated with type 2 diabetes in both populations ().
Association of socioeconomic status and non-European ancestry with type 2 diabetes is not confounded by BMI