Comprehensive Genetic Analysis of the Human Lipidome Identifies Novel Loci Controlling Lipid Homeostasis
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Abstract: Lipids comprise thousands of individual species, spanning many classes and subclasses and are integral to cellular signalling, metabolism and function. Genome-wide association studies (GWAS) of lipid species can provide novel insights into human physiology, inborn errors of metabolism andmechanisms for complex traits and diseases. We integrated lipidomics and genomics to unravel the genetic architecture of lipid metabolism andidentify genetic variants associated with lipid species that are putatively in the mechanistic pathway to coronary artery disease.
We identified 737 independent loci associations with these lipid species (509 novel). Associations between independent lipid-loci with coronary atherosclerosis were assessed in 456,000 individuals from the UK Biobank. Of the 53 lipid-loci that showed evidence of association (P<1×10-3), 43 loci were associated with at least one lipid endophenotype.
Using the same data, we examined the associations of plasma lipid species with Alzheimer’s disease and APOE genotypes to demonstrate that lipid species partially mediate the Alzheimer’s disease risk resulting from inherited APOE genotypes.
These findings illustrate the value of integrative biology to investigate the genetics and lipid metabolism in the aetiology of coronary artery disease and Alzheimer’s disease, with implications for other complex diseases.
Speaker
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Professor Peter Meikle
Baker Heart and Diabetes Institute
Professor Peter Meikle is Head of the Systems Biology Domain, Co-Lead of the Obesity and Lipids Program and Head of the Metabolomics Laboratory at the Baker Heart and Diabetes Institute. He is co-Director of the Australian Cardiovascular Alliance, Precision Medicine Flagship and was recently appointed Head of the Baker Department of Cardiovascular Research, Translation and Implementation at La Trobe University…About the speaker: Professor Peter Meikle is Head of the Systems Biology Domain, Co-Lead of the Obesity and Lipids Program and Head of the Metabolomics Laboratory at the Baker Heart and Diabetes Institute. He is co-Director of the Australian Cardiovascular Alliance, Precision Medicine Flagship and was recently appointed Head of the Baker Department of Cardiovascular Research, Translation and Implementation at La Trobe University. His research has a focus on the dysregulation of lipid metabolism associated with metabolic diseases including obesity, diabetes, cardiovascular and Alzheimer’s disease, and its relationship to the pathogenesis of these disease states. This work is leading to new approaches to early diagnosis and risk assessment, and to the development of new lipid modulating therapies for chronic disease.
