Biological  significance of genetic variants associated with Apolipoprotein E (ApoE) identified by Genome-Wide Association Studies

Presenter: Ghazaleh Fatemifar, University College London

Author: Ghazaleh Fatemifar

Apolipoprotein E (ApoE) is found in chylomicron and intermediate density lipoprotein. It is predominantly synthesised in the liver, but is also found in other tissues such as the brain, kidney and spleen. Initially, ApoE was established for its significance in lipoprotein metabolism and cardiovascular disease. However, it has also been linked to other complex diseases such as Alzheimer’s. In order to identify genetic variants associated with circulating ApoE, we performed a population based genome-wide association study using 5208 individuals from the English Longitudinal Study of Ageing and 1352 individuals from the Fenland Study. We tested 1.4 million Single Nucleotide Polymorphisms common to both studies and controlled for age and sex. Results from the two studies were combined using a fixed effects inverse variance meta-analysis. Three independent loci were associated with circulating ApoE at genome-wide significance (P<5×10-8). Together these associations explained 10% of the variation in ApoE. An unweighted allelic score of the independently associated variants was tested for association with several biomarkers (high/low-density lipoprotein and Triglycerides), inflammatory marker C-reactive protein and cognition variables (verbal fluency and total memory). Associations were identified between ApoE allelic score and all biomarkers (p<0.01). Conversely, no association was established between ApoE allelic score and C-reactive protein or cognition variables. We believe the lack of association is as a result of power. Therefore, we aim to examine the association of the ApoE allelic score with inflammatory markers and cognitive function using data available in Understanding Society in order to complete an appropriately powered analysis of ApoE.