Genome-wide analysis of oxylipins and oxylipin profiles in a pediatric population
BackgroundOxylipins 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 identi...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Nutrition |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnut.2023.1040993/full |
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| author | Teresa Buckner Teresa Buckner Randi K. Johnson Randi K. Johnson Lauren A. Vanderlinden Patrick M. Carry Patrick M. Carry Alex Romero Suna Onengut-Gumuscu Wei-Min Chen Soojeong Kim Oliver Fiehn Brigitte I. Frohnert Tessa Crume Wei Perng Katerina Kechris Marian Rewers Jill M. Norris |
| author_facet | Teresa Buckner Teresa Buckner Randi K. Johnson Randi K. Johnson Lauren A. Vanderlinden Patrick M. Carry Patrick M. Carry Alex Romero Suna Onengut-Gumuscu Wei-Min Chen Soojeong Kim Oliver Fiehn Brigitte I. Frohnert Tessa Crume Wei Perng Katerina Kechris Marian Rewers Jill M. Norris |
| author_sort | Teresa Buckner |
| collection | DOAJ |
| description | BackgroundOxylipins 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.MethodsWe 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: p < 5×10−8).ResultsThe SNP rs143070873 was associated with (p < 5×10−8) the LA-related oxylipin 9-HODE, and rs6444933 (downstream of CLDN11) was associated with the LA-related oxylipin 13 S-HODE. A locus between MIR1302-7 and LOC100131146, rs10118380 and an intronic variant in TRPM3 were associated with the ARA-related oxylipin 11-HETE. These loci are involved in inflammatory signaling cascades and interact with PLA2, an initial step to oxylipin biosynthesis.ConclusionGenetic loci involved in inflammation and oxylipin metabolism are associated with oxylipin levels. |
| first_indexed | 2024-04-09T21:21:21Z |
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| language | English |
| last_indexed | 2024-04-09T21:21:21Z |
| publishDate | 2023-03-01 |
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| series | Frontiers in Nutrition |
| spelling | doaj.art-1fe4b1d6ea3a4185b725567210cde7052023-03-28T05:22:47ZengFrontiers Media S.A.Frontiers in Nutrition2296-861X2023-03-011010.3389/fnut.2023.10409931040993Genome-wide analysis of oxylipins and oxylipin profiles in a pediatric populationTeresa Buckner0Teresa Buckner1Randi K. Johnson2Randi K. Johnson3Lauren A. Vanderlinden4Patrick M. Carry5Patrick M. Carry6Alex Romero7Suna Onengut-Gumuscu8Wei-Min Chen9Soojeong Kim10Oliver Fiehn11Brigitte I. Frohnert12Tessa Crume13Wei Perng14Katerina Kechris15Marian Rewers16Jill M. Norris17Department of Epidemiology, Colorado School of Public Health, Anschutz Medical Campus, Aurora, CO, United StatesDepartment of Kinesiology, Nutrition, and Dietetics, University of Northern Colorado, Greeley, CO, United StatesDepartment of Epidemiology, Colorado School of Public Health, Anschutz Medical Campus, Aurora, CO, United StatesDepartment of Biomedical Informatics, CU School of Medicine, Anschutz Medical Campus, Aurora, CO, United StatesDepartment of Epidemiology, Colorado School of Public Health, Anschutz Medical Campus, Aurora, CO, United StatesDepartment of Epidemiology, Colorado School of Public Health, Anschutz Medical Campus, Aurora, CO, United StatesColorado Program for Musculoskeletal Research, Department of Orthopedics, CU School of Medicine, Anschutz Medical Campus, Aurora, CO, United StatesDepartment of Biomedical Informatics, CU School of Medicine, Anschutz Medical Campus, Aurora, CO, United StatesCenter for Public Health Genomics, University of Virginia, Charlottesville, VA, United StatesCenter for Public Health Genomics, University of Virginia, Charlottesville, VA, United StatesDepartment of Health Administration, Dongseo University, Busan, Republic of KoreaNIH-West Coast Metabolomics Center, University of California-Davis, Davis, CA, United StatesThe Barbara Davis Center for Diabetes, CU School of Medicine, Anschutz Medical Campus, Aurora, CO, United StatesDepartment of Epidemiology, Colorado School of Public Health, Anschutz Medical Campus, Aurora, CO, United StatesDepartment of Epidemiology, Colorado School of Public Health, Anschutz Medical Campus, Aurora, CO, United StatesDepartment of Biostatistics and Informatics, Colorado School of Public Health, Anschutz Medical Campus, Aurora, CO, United StatesThe Barbara Davis Center for Diabetes, CU School of Medicine, Anschutz Medical Campus, Aurora, CO, United StatesDepartment of Epidemiology, Colorado School of Public Health, Anschutz Medical Campus, Aurora, CO, United StatesBackgroundOxylipins 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.MethodsWe 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: p < 5×10−8).ResultsThe SNP rs143070873 was associated with (p < 5×10−8) the LA-related oxylipin 9-HODE, and rs6444933 (downstream of CLDN11) was associated with the LA-related oxylipin 13 S-HODE. A locus between MIR1302-7 and LOC100131146, rs10118380 and an intronic variant in TRPM3 were associated with the ARA-related oxylipin 11-HETE. These loci are involved in inflammatory signaling cascades and interact with PLA2, an initial step to oxylipin biosynthesis.ConclusionGenetic loci involved in inflammation and oxylipin metabolism are associated with oxylipin levels.https://www.frontiersin.org/articles/10.3389/fnut.2023.1040993/fulloxylipininflammationpediatricgenome-wide association studypolyunsaturated fatty acidslipid mediators |
| spellingShingle | Teresa Buckner Teresa Buckner Randi K. Johnson Randi K. Johnson Lauren A. Vanderlinden Patrick M. Carry Patrick M. Carry Alex Romero Suna Onengut-Gumuscu Wei-Min Chen Soojeong Kim Oliver Fiehn Brigitte I. Frohnert Tessa Crume Wei Perng Katerina Kechris Marian Rewers Jill M. Norris Genome-wide analysis of oxylipins and oxylipin profiles in a pediatric population Frontiers in Nutrition oxylipin inflammation pediatric genome-wide association study polyunsaturated fatty acids lipid mediators |
| title | Genome-wide analysis of oxylipins and oxylipin profiles in a pediatric population |
| title_full | Genome-wide analysis of oxylipins and oxylipin profiles in a pediatric population |
| title_fullStr | Genome-wide analysis of oxylipins and oxylipin profiles in a pediatric population |
| title_full_unstemmed | Genome-wide analysis of oxylipins and oxylipin profiles in a pediatric population |
| title_short | Genome-wide analysis of oxylipins and oxylipin profiles in a pediatric population |
| title_sort | genome wide analysis of oxylipins and oxylipin profiles in a pediatric population |
| topic | oxylipin inflammation pediatric genome-wide association study polyunsaturated fatty acids lipid mediators |
| url | https://www.frontiersin.org/articles/10.3389/fnut.2023.1040993/full |
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