Faculty, Staff and Student Publications
Publication Date
1-9-2025
Journal
Human Genetics and Genomics Advances
Abstract
Bioactive fatty acid-derived oxylipin molecules play key roles mediating inflammation and oxidative stress. Circulating levels of fatty acids and oxylipins are influenced by environmental and genetic factors; characterizing the genetic architecture of bioactive lipids could yield new insights into underlying biology. We performed a genome-wide association study (GWAS) of 81 fatty acids and oxylipins in 11,584 Hispanic Community Health Study/Study of Latinos (HCHS/SOL) participants with genetic and lipidomic data measured at study baseline (58.6% female, mean age = 46.1 years (standard deviation 13.8)). Additionally, given the effects of central obesity on inflammation, we examined interactions with waist circumference using two-degree-of-freedom joint tests. Thirty-three of the 81 oxylipins and fatty acids were significantly heritable (heritability range: 0-32.7%). Forty (49.4%) oxylipins and fatty acids had at least one genome-wide significant (p < 6.94E-11) variant resulting in 19 independent genetic loci. Six loci (lead variant minor allele frequency [MAF] range: 0.08-0.50), including desaturase-encoding FADS and OATP1B1 transporter protein-encoding SLCO1B1, exhibited associations with two or more fatty acids and oxylipins. At several of these loci, there was evidence of colocalization of the top variant across fatty acids and oxylipins. The remaining loci were only associated with one oxylipin or fatty acid and included several CYP loci. We also identified an additional rare variant (MAF = 0.002) near CARS2 in two-degree-of-freedom tests. Our analyses revealed shared and distinct genetic architecture underlying fatty acids and oxylipins, providing insights into genetic factors and motivating work to characterize these compounds and elucidate their roles in disease.
Keywords
Humans, Genome-Wide Association Study, Oxylipins, Hispanic or Latino, Female, Male, Fatty Acids, Middle Aged, Adult, Polymorphism, Single Nucleotide, Delta-5 Fatty Acid Desaturase, Fatty Acid Desaturases, Gene Frequency, White
DOI
10.1016/j.xhgg.2024.100390
PMID
39644095
PMCID
PMC11751521
PubMedCentral® Posted Date
12-6-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Included in
Medical Genetics Commons, Medicine and Health Commons, Public Health Commons, Race and Ethnicity Commons
