Abstract 1407 Comprehensive Genetic Analysis of the Human Lipidome Identifies Novel Loci Controlling Lipid Homeostasis with Links to Cardiometabolic Disease and Alzheimer's Disease

Dysregulation of lipid metabolism is as an important –and modifiable– risk factor for multiple diseases, including type 2 diabetes, cardiovascular disease and age-related dementia. While the metabolic pathways of lipids are well characterised, dysregulation of these pathways due to environmental and genetic influences is not well understood. To address this issue, we have applied an integrative approach to link genetic variants with altered lipid metabolism and metabolic disease. Using lipidomic profiling data from 4,492 genotyped individuals from the Busselton Family Health Study, we performed genome-wide association analysis of 596 lipid species and 33 lipid classes using linear-mixed models, correcting for age, sex, their interactions. Validation of genome-wide significant associations was supported by replication and meta-analyses in the Australian Imaging, Biomarker NIA supported the Alzheimer's Disease Metabolomics Consortium which is a part of NIA's national initiatives AMP-AD and M2OVE-AD.