Genetic analyses of circulating PUFA-derived mediators identifies heritable dihydroxyeicosatrienoic acid species
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Published version
Author(s)
McGurk, Kathryn A
Farrell, Laura
Kendall, Alexandra C
Keavney, Bernard D
Nicolaou, Anna
Type
Journal Article
Abstract
Estimates of heritability are the first step in identifying a trait with substantial variation due to genetic factors. Large-scale genetic analyses can identify the DNA variants that influence the levels of circulating lipid species and the statistical technique Mendelian randomisation can use these DNA variants to address potential causality of these lipids in disease. We estimated the heritability of plasma eicosanoids, octadecanoids and docosanoids to identify those lipid species with substantial heritability. We analysed plasma lipid mediators in 31 White British families (196 participants) ascertained for high blood pressure and deeply clinically and biochemically phenotyped over a 25-year period. We found that the dihydroxyeicosatrienoic acid (DHET) species, 11,12-DHET and 14,15-DHET, products of arachidonic acid metabolism by cytochrome P450 (CYP) monooxygenase and soluble epoxide hydrolase (sEH), exhibited substantial heritability (h2 = 33%−37%; Padj<0.05). Identification of these two heritable bioactive lipid species allows for future large-scale, targeted, lipidomics-genomics analyses to address causality in cardiovascular and other diseases.
Date Issued
2022-06-01
Date Acceptance
2022-04-20
Citation
Prostaglandins and Other Lipid Mediators, 2022, 160
ISSN
1098-8823
Publisher
Elsevier
Journal / Book Title
Prostaglandins and Other Lipid Mediators
Volume
160
Copyright Statement
© 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
License URL
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000799000100001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Cell Biology
Heritability
Genetics
Lipidomics
Eicosanoids
Dihydroxyeicosatrienoic acid
CORONARY-ARTERY-DISEASE
CYTOCHROME P450-DERIVED EICOSANOIDS
GENOME-WIDE ASSOCIATION
5-LIPOXYGENASE PATHWAY
ARACHIDONIC-ACID
FATTY-ACIDS
PRESSURE
PLASMA
POLYMORPHISM
EXPRESSION
Publication Status
Published
Article Number
ARTN 106638