title: An investigation of gene-diet interactions on lipid-related traits in different ethnic groups
Creators: name: Wuni, Ramatu
Publisher: name: University of Reading
Year: 2025

description: 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.