Abstract 16367: Genetically Elevated Body Mass Index Leaves Global Imprints on the Systemic Metabolite Profile in Young Adults

Abstract

Introduction: Elevated body mass index (BMI) due to common genetic variants has been linked with the risk for future ischemic heart disease, yet it remains unclear how this association is mediated. Hypothesis: We assessed whether genetic predisposition to obesity is associated with increased cardiovascular risk factor levels and the global metabolite profile in apparently healthy young adults.

Method: A genetic risk score composed of 32 variants was tested against cardiovascular risk factors and the serum metabolome profile in 6,774 young adults (mean age 31) from two population-based cohorts in Finland.

Results: The genetic risk score was associated with increased BMI (P=1x10-30) and had effects on blood pressure, insulin resistance index and inflammatory markers as well as liver enzymes (P<0.0005). Genetically elevated BMI was also associated with an atherogenic lipoprotein profile characterized by elevated VLDL and decreased large HDL lipid levels while effects on LDL levels were only significant in women. The strongest metabolite abnormalities caused by the obesity-related genetic variants were found for circulating concentrations of branched-chain and aromatic amino acids. These amino acids have recently been associated with the risk for future diabetes and our findings suggest that obesity is directly contributing to mediate this associations already in early adulthood.

Conclusion: Our results suggest that increased BMI due to genetic predisposition has a diverse impact on the global metabolite profile in young adults and that the association of BMI with the risk for future heart disease is partly transmitted through established metabolic risk factors. These findings elucidate the causal role of high BMI in the general population and emphasize risk factor monitoring in individuals genetically susceptible to obesity.