Type 2 diabetes heritability in the Tehran families: Tehran cardiometabolic genetic study

Introduction: Type 2 diabetes, as a complex disorder, is one of the most prevalent endocrine disorders.  Importantly, the extent of familial aggregation and heritability in Iran is unknown. The aim of the present study was to determine type 2 diabetes heritability in the Tehran families. Materials and Methods: The current research comprises 1691 diabetic and 12050 non-diabetic individuals over 20 years who are participants in the Tehran Cardiometabolic Genetic Study (TCGS). In this research, the BGLR, gap, and S.A.G.E tools were used to conduct familial aggregation, family-based heritability, and segregation analysis. Results: Out of 13741 subjects, 45% were female, and 55% were male in 2594 constituent pedigrees. The results of intra-family correlation showed that there is a higher correlation among siblings (ICCbrother-sister = 0.26, ICCbrother-brother =0.16, ICCsister-sister =0.14) than mother-offspring (ICCmother-offsprings = 0.13) followed by father-son (ICCfather-son = 0.05). Besides, the results of logistic regression showed that the chances of developing diabetes are higher in people whose at least one parent had diabetes (OR=4.16). The heritability rate in this population was about 65% (SE=0.034). The segregation analysis showed that type 2 diabetes in this community follows a polygenic pattern. Conclusion: The heritability of type 2 diabetes with a polygenic pattern in Iran is higher than the global average. Type 2 diabetes is transmitted equally to siblings, and in terms of family history, parents are the most important risk factor for the disease. According to the findings of this research, it is recommended to shift the level of prevention from the individual to the family level in society when making health-system policy decisions.