Investigating the Potential Effect of Consanguinity on Type 2 Diabetes Susceptibility in a Saudi Population

Background: Several studies suggested association between consanguinity and risk of developing Type 2 Diabetes (T2D). Aim: To examine mechanisms by which consanguinity might increase the risk of T2D in a Saudi population. Methodology: 362 adult male participants were recruited, 179 were T2D patients and 183 healthy participants were siblings of recruited patients. Severity was assessed in patients by recording age at diagnosis. Diabetes risk in healthy subjects was inspected by measuring their body mass index (BMI), fasting blood glucose (FBG), and waist circumference. Extended pedigrees were constructed to calculate inbreeding coefficients. 23 Single Nucleotide Polymorphisms (SNPs) incurring higher risk of T2D were genotyped. All subjects were interviewed to complete food frequency and physical activity questionnaires to provide information on environmental variation between participants. Results: Significant inverse association was detected between inbreeding coefficients and age at diagnosis accounting for environmental covariates (β: -0.572 P-value: 0.012). In 42 families, we were able to recruit 2 healthy siblings from each. Pearson’s correlation coefficient of FBG between siblings was 0.317 (P= 0.04). Correlations between siblings’ FBG increased with increased range of consanguinity suggesting a stronger genetic influence leading to lower variation of FBG between siblings. The effect of consanguinity on variation of FBG was further assessed by fitting a regression line and controlling for difference in age, calorific intake, and level of physical activity (β: -0.118 P-value: 0.024). No significant associations were detected between number of loci identical for risk alleles and age at diagnosis, BMI, FBG or waist circumference. An association of marginal significant was detected between age at diagnosis and total number of risk alleles when accounting for parental history of diabetes and inbreeding coefficients (β:-0.399 P: 0.052). Conclusion: Study’s findings suggest consanguinity might increase risk of T2D by earlier development of the disease, and by strengthening possible genetic effect on FBG.