Abstract/Summary

Cardiometabolic diseases including cardiovascular diseases (CVDs) remain a threat to global public health, placing a significant burden on low- and middle-income countries. Among the risk factors for CVDs is an altered blood lipid profile, usually characterised by a rise in the concentration of triglycerides (TG) or low-density lipoprotein cholesterol (LDL-C) and a reduction in the concentration of high-density lipoprotein cholesterol (HDL-C). Lipid-related traits such as CVDs are known to be impacted by environmental factors including dietary intake. However, evidence from genetic association studies indicates that genetic variants play a role in the development of these traits. Therefore, investigating how gene-diet interactions impact on lipid-related traits could help to improve our understanding of the underlying pathophysiology and the development of precision nutrition strategies for the prevention and management of these conditions. Gene-diet interaction studies have been extended to cover previously under-represented populations, but there is still limited research in some developing countries. The main aim of this PhD work was to investigate the association of single nucleotide polymorphisms (SNPs) as a genetic risk score (GRS) with lipid-related traits in different ethnic groups. The interaction of the GRS with dietary factors on lipid-related traits was also assessed. Additionally, the association between dairy intake, a source of saturated fat, on cardiometabolic risk factors was investigated. Finally, factors that need to be considered to facilitate the translation of nutrigenetics to personalised and precision nutrition for cardiometabolic health in diverse ethnic groups were explored. This thesis included seven studies: a review of cholesteryl ester transfer protein (CETP) gene-diet interactions on lipid-related outcomes; three cross-sectional cohort studies [the Obesity, Lifestyle and Diabetes in Brazil (BOLD) study, Brazilian young adults, n=190; the Chennai Urban Rural Epidemiological Study (CURES), Asian Indian adults, n=1,033; and the Study of Obesity, Nutrition, Genes and Social factors (SONGS), Peruvian young adults, n=468]; a case-control study (CURES, Asian Indian adults, n=497); a systematic review of gene-lifestyle interactions on cardiometabolic disease-related traits in Latin American and Caribbean populations; and a review focusing on the barriers in translating existing nutrigenetics insights to precision nutrition for cardiometabolic health in ethnically diverse populations. Statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS) software (version 28; SPSS Inc., Chicago, IL, USA) and the R software version 4.3.1. Significant GRS-saturated fatty acid (SFA) intake interactions were observed in the Brazilian and Asian Indian populations, impacting on TG:HDL-C ratio (Pinteraction=0.03) and waist circumference (Pinteraction=0.006), respectively. A significant GRS- total fat intake interaction on TG:HDL-C ratio was also observed in the Brazilian population (Pinteraction=0.03). In the Peruvian population, a significant GRS-carbohydrate intake interaction on the concentration of HDL-C was observed (Pinteraction=0.0007). Also in the Peruvian population, participants with a high GRS, had lower concentrations of HDL-C across tertiles of glycaemic load (Ptrend=0.017). In summary, the findings of this thesis add to the field of nutrigenetics by showing the presence of genetic heterogeneity in gene-diet interactions on lipid-related traits in different ethnic groups. These findings will contribute to improved understanding of how genetic and dietary factors interact to alter the susceptibility to CVDs in different ethnic groups. Replication of the findings in large scale longitudinal and dietary intervention studies is required prior to being considered for personalised dietary guidelines.