Approved Research

Metabolic Syndrome-Associated Genes and Progression to Type 2 Diabetes and Cardiovascular Disease in Adults

Lay summary

Metabolic syndrome (MetS) is a major global non-communicable health hazard and has seen unprecedented rise in the recent decades, associated with the rapidly increasing obesity prevalence. MetS, a constellation of cardiovascular disease (CVD) and type 2 diabetes (T2D) risk factors, is characterized by abdominal obesity, insulin resistance, hypertension, and hyperlipidaemia. T2D has become one of the major causes of premature illness and death mainly through this increased risk of CVD which is responsible for up to 80 per cent of these deaths.

Numerous research studies have widely investigated on the occurrence of individual risk factors which comprise MetS and their associations, such as dyslipidaemia and diabetes. Several investigations from linkage analysis, candidate gene approach and genome-wide association studies (GWAS) have likewise focused on the causative genetic aspects and established heritability of a single MetS component. A recent (2019) GWAS on MetS was performed from the UK Biobank wherein 93 independent loci have been identified to be associated with MetS, 80 of which were novel. Seven genes of particular interest were noted: five (WDR48, KLF14, NAADL1, GADD45G, and OR5R1) were not previously associated with any MetS component; and two (SNX10, C5orf67) were associated with all five MetS components in previous studies.

Based on current evidence, research studies are focused on MetS individual components and not as a broader entity. There is a huge scarcity of inquiries regarding examining this disease condition as a whole rather than separately. In addition, T2D and CVDs have undoubtedly a significant worldwide impact on mortality, and health and economic burden. Hence a study on the overlap of genetics and T2D and CVD progression warrants significant contribution to the call for further much-needed breakthroughs on this condition. This study aims to elucidate on MetS-associated genotypes which are more likely to predispose individuals in developing T2D and/or CVD. The expected duration of this investigation is up to 36 months.

Individuals with conditions known to affect obesity and T2D other than MetS-associated genes will not be included, as well as those who are metabolically- or immuno-compromised or with serious illnesses. Confounding factors such as pharmacotherapy, other interventions (e.g. bariatric surgery), physical activity level, and diet will be considered.