Heritability and Genetics of Type 2 Diabetes Mellitus in Sub-Saharan Africa: A Systematic Review and Meta-Analysis.

The pattern and characteristics of T2DM heritability in SSA are preference for maternal aggregation, higher among first degree compared to second-degree relatives; early age-onset (<50 years), and inherited abnormalities of beta-cell function/mass. The overall prevalence of T2DM was 28.2% for the population with a positive family history (PFH) and 11.2% for the population with negative family history (NFH). The pooled odds ratio of the impact of PFH on T2DM was 3.29 (95% CI: 2.40-4.52). Overall, 28 polymorphisms in 17 genes have been investigated in relation with T2DM in SSA. Almost all studies used the candidate gene approach with most (45.8%) of genetic studies published between 2011 and 2015. Polymorphisms in ABCC8, Haptoglobin, KCNJ11, ACDC, ENPP1, TNF-α, and TCF7L2 were found to be associated with T2DM, with overlapping effect on specific cardiometabolic traits. Genome-wide studies identified ancestry-specific signals (AGMO-rs73284431, VT11A-rs17746147, and ZRANB3) and TCF7L2-rs7903146 as the only transferable genetic risk variants to SSA population. TCF7L2-rs7903146 polymorphism was investigated in multiple studies with consistent effects and low-moderate statistical heterogeneity. Effect sizes were modestly strong [odds ratio = 6.17 (95% CI: 2.03-18.81), codominant model; 2.27 (95% CI: 1.50-3.44), additive model; 1.75 (95% CI: 1.18-2.59), recessive model]. Current evidence on the heritability and genetic markers of T2DM in SSA populations is limited and largely insufficient to reliably inform the genetic architecture of T2DM across SSA regions.