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Signalling lipids of the N-acyl ethanolamine (NAE) and ceramide (CER) classes have emerged as potential biomarkers of cardiovascular disease (CVD). We sought to establish the heritability of plasma NAEs (including the endocannabinoid anandamide) and CERs, to identify common DNA variants influencing the circulating concentrations of the heritable lipids, and assess causality of these lipids in CVD using 2-sample Mendelian randomization (2SMR). Nine NAEs and 16 CERs were analyzed in plasma samples from 999 members of 196 British Caucasian families, using targeted ultra-performance liquid chromatography with tandem mass spectrometry. All lipids were significantly heritable (h2 = 36-62%). A missense variant (rs324420) in the gene encoding the enzyme fatty acid amide hydrolase (FAAH), which degrades NAEs, associated at genome-wide association study (GWAS) significance (P 

Original publication

DOI

10.1093/hmg/ddab002

Type

Journal article

Journal

Human molecular genetics

Publication Date

04/2021

Volume

30

Pages

500 - 513

Addresses

Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9NT, UK.

Keywords

Humans, Cardiovascular Diseases, Genetic Predisposition to Disease, Ethanolamines, Ceramides, Case-Control Studies, Polymorphism, Single Nucleotide, Middle Aged, Female, Male, Genome-Wide Association Study, Mendelian Randomization Analysis, Biomarkers, Lipidomics