Heritability and Genetics of Type 2 Diabetes Mellitus in Sub-Saharan Africa: A Systematic Review and Meta-Analysis
Evans Asamoah Adu, Christian Obirikorang, Emmanuel Acheampong, Max Efui Annani-Akollor, Edwin Ferguson Laing, Eddie‐Williams Owiredu, Enoch Odame Anto
Abstract
Objectives . Sub-Saharan Africa (SSA) is observing an accelerating prevalence rate of type 2 diabetes mellitus (T2DM) influenced by gene-environment interaction of modifiable and nonmodifiable factors. We conducted a systematic review and meta-analysis on the heritability and genetic risk of T2DM in SSA. Methods . We reviewed all published articles on T2DM in SSA between January 2000 and December 2019 and available in PubMed, Scopus, and Web of Science. Studies that reported on the genetics and/or heritability of T2DM or indicators of glycaemia were included. Data extracted included the study design, records of family history, pattern and characteristics of inheritance, genetic determinants, and effects estimates. Results . 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 [<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mtext>odds</mml:mtext><mml:mtext> </mml:mtext><mml:mtext>ratio</mml:mtext><mml:mo>=</mml:mo><mml:mn>6.17</mml:mn></mml:math> (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.