Determinants and correlates of lipid profiles and their relation with human health

Abstract

Lipids are one of the most abundant and diverse molecules in the human body; our lipid profile consists of thousands of unique lipids. Everyone's profile is unique, and is the result of internal processes, genetics, and the external environment. As such, it provides a wealth of information on someone's past exposures, current health, and future disease risk. Indeed, lipids have been linked to various diseases, including cardiometabolic and neurological diseases. <br/>

Despite the growing interest in lipids, much remains unknown about this relatively new field, including the determinants of circulating lipids and their effects on human health. In particular, there is a need for cohort studies covering the disease continuum, rather than focusing on a single condition. This thesis uses data from the community-based Rhineland Study to (I) study genetic and environmental factors influencing lipids, and (II) evaluate the relation between lipids and human health. <br/>

We reveal novel gene-lipid loci in a genome-wide association study (GWAS), which were validated using gene expression data. Using this data, we provide new insights into the heritability of lipids. Furthermore, we show the impact of toxic human-made chemicals in a study relating per- and polyfluoralkyl substances (PFAS) to lipids. Specifically, even low exposure levels of these toxic chemicals were found to be related to a potentially harmful lipid profile – i.e. a higher lipid content of lipoproteins. <br/>

Additionally, we found that a lipid's fatty acid tail was crucial for its effect on biological ageing and brain health. For example, 16-carbon carrying lipids were related to a higher biological age and worse brain health. In contrast, dairy-derived odd-chained fatty acids seemed beneficial. Importantly, we also found sex-specific effects of certain lipids as ceramides were related more strongly to white matter lesions in women than in men. <br/>

This thesis provides important insights into determinants of lipids and their health impacts, highlighting the potential in improving disease understanding, prevention and treatment.