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

Teresa Buckner; Randi K Johnson; Lauren A Vanderlinden; 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

doi:10.3389/fnut.2023.1040993

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

Front Nutr. 2023 Mar 28:10:1040993. doi: 10.3389/fnut.2023.1040993. eCollection 2023.

Authors

Teresa Buckner^{1

2}, Randi K Johnson^{1

3}, Lauren A Vanderlinden¹, Patrick M Carry^{1

4}, Alex Romero³, Suna Onengut-Gumuscu⁵, Wei-Min Chen⁵, Soojeong Kim⁶, Oliver Fiehn⁷, Brigitte I Frohnert⁸, Tessa Crume¹, Wei Perng¹, Katerina Kechris⁹, Marian Rewers⁸, Jill M Norris¹

Affiliations

¹ Department of Epidemiology, Colorado School of Public Health, Anschutz Medical Campus, Aurora, CO, United States.
² Department of Kinesiology, Nutrition, and Dietetics, University of Northern Colorado, Greeley, CO, United States.
³ Department of Biomedical Informatics, CU School of Medicine, Anschutz Medical Campus, Aurora, CO, United States.
⁴ Colorado Program for Musculoskeletal Research, Department of Orthopedics, CU School of Medicine, Anschutz Medical Campus, Aurora, CO, United States.
⁵ Center for Public Health Genomics, University of Virginia, Charlottesville, VA, United States.
⁶ Department of Health Administration, Dongseo University, Busan, Republic of Korea.
⁷ NIH-West Coast Metabolomics Center, University of California-Davis, Davis, CA, United States.
⁸ The Barbara Davis Center for Diabetes, CU School of Medicine, Anschutz Medical Campus, Aurora, CO, United States.
⁹ Department of Biostatistics and Informatics, Colorado School of Public Health, Anschutz Medical Campus, Aurora, CO, United States.

Abstract

Background: 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.

Methods: 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: p < 5×10^-8).

Results: The 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.

Conclusion: Genetic loci involved in inflammation and oxylipin metabolism are associated with oxylipin levels.

Keywords: genome-wide association study; inflammation; lipid mediators; oxylipin; pediatric; polyunsaturated fatty acids.

Abstract

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