AUTHOR=Buckner Teresa , Johnson Randi K. , Vanderlinden Lauren A. , Carry Patrick M. , Romero Alex , Onengut-Gumuscu Suna , Chen Wei-Min , Kim Soojeong , Fiehn Oliver , Frohnert Brigitte I. , Crume Tessa , Perng Wei , Kechris Katerina , Rewers Marian , Norris Jill M. 

TITLE=Genome-wide analysis of oxylipins and oxylipin profiles in a pediatric population

JOURNAL=Frontiers in Nutrition

VOLUME=10

YEAR=2023

URL=https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2023.1040993

DOI=10.3389/fnut.2023.1040993

ISSN=2296-861X

ABSTRACT=<sec><title>Background</title><p>Oxylipins are inflammatory biomarkers derived from omega-3 and-6 fatty acids implicated in inflammatory diseases but have not been studied in a genome-wide association study (GWAS). The aim of this study was to identify genetic loci associated with oxylipins and oxylipin profiles to identify biologic pathways and therapeutic targets for oxylipins.</p></sec><sec><title>Methods</title><p>We conducted a GWAS of plasma oxylipins in 316 participants in the Diabetes Autoimmunity Study in the Young (DAISY). DNA samples were genotyped using the TEDDY-T1D Exome array, and additional variants were imputed using the Trans-Omics for Precision Medicine (TOPMed) multi-ancestry reference panel. Principal components analysis of 36 plasma oxylipins was used to capture oxylipin profiles. PC1 represented linoleic acid (LA)- and alpha-linolenic acid (ALA)-related oxylipins, and PC2 represented arachidonic acid (ARA)-related oxylipins. Oxylipin PC1, PC2, and the top five loading oxylipins from each PC were used as outcomes in the GWAS (genome-wide significance: <italic>p</italic> &lt; 5×10<sup>−8</sup>).</p></sec><sec><title>Results</title><p>The SNP rs143070873 was associated with (p &lt; 5×10<sup>−8</sup>) the LA-related oxylipin 9-HODE, and rs6444933 (downstream of <italic>CLDN11</italic>) was associated with the LA-related oxylipin 13 S-HODE. A locus between <italic>MIR1302-7</italic> and <italic>LOC100131146</italic>, rs10118380 and an intronic variant in <italic>TRPM3</italic> were associated with the ARA-related oxylipin 11-HETE. These loci are involved in inflammatory signaling cascades and interact with <italic>PLA2</italic>, an initial step to oxylipin biosynthesis.</p></sec><sec><title>Conclusion</title><p>Genetic loci involved in inflammation and oxylipin metabolism are associated with oxylipin levels.</p></sec>