{"doi":"10.3390/nu17061089","title":"The Effect of Fatty Acid Desaturase on Cardiovascular Lipid Biomarkers Depends on Circulating ω-3 and ω-6 Polyunsaturated Fatty Acids in the UK Biobank","abstract":"Objectives: The objective of this study is to outline a framework for how fatty acids may be acting as mediators/suppressors and/or moderators of an individual’s genetic predisposition for cardiovascular lipid biomarkers. Methods: All UK Biobank participants with demographic and lifestyle variables, circulating cardiovascular lipids, and NMR-measured fatty acid data collected at the baseline visit (N = 229,859) were included in analyses. We fit four separate linear regression models, one for each of the following common measures of cardiovascular lipids: total cholesterol, HDL-c, LDL-c, and total triglycerides. Each model predicted cardiovascular lipids by an individual’s FADS (a well-known fatty acid desaturase gene complex) haplotype, with the addition of individual ω-3 (DHA, non-DHA, and total), ω-6 (LA, non-LA, and total), or SFA factors as additive (mediation/suppression) or using an interaction term (with FADS) (moderation). All models were adjusted for a wide range of demographic and medical history variables and evaluated against a Bonferroni-adjusted significance level (p < 8.9 × 10−4). Results: Across 56 models (four lipids × seven FAs × two conceptual models (mediation/suppression and moderation)), we found evidence of 19 moderation, 12 mediation, and 16 suppression effects of the FADS–lipid relationship. For example, adjusting for circulating DHA levels as a mediator, the association of the genotype with HDL-c substantially lessened for both minor genotypes reflecting >122% mediation of the association of FADS by DHA. Additionally, we found evidence that LDL-c is moderated, to some extent, by all fatty acid measures. Conclusions: This analysis demonstrates that an individual’s fatty acid profile can act as a mediator/suppressor or moderator of the association of the FADS genotype and various cardiovascular biomarkers. Future work is necessary to expand this cross-sectional examination to determine directionality and temporality of the mediation and moderation evidence presented. This research has been conducted using the UK Biobank Resource under Application Number 85092.","journal":"Nutrients","year":2025,"id":552071,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9073,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":542704,"name":"Jason Westra","orcid":"0000-0002-4754-1395","position":1,"is_corresponding":false},{"id":305423,"name":"Nathan Tintle","orcid":"0000-0003-1447-9107","position":2,"is_corresponding":false},{"id":415356,"name":"Gregory C. Shearer","orcid":"0000-0003-4722-9163","position":3,"is_corresponding":false},{"id":1447963,"name":"Carmen Arrington","orcid":"0000-0001-7403-5976","position":0,"is_corresponding":true}],"reference_count":75,"raw_metadata":null,"created_at":"2026-07-19T02:54:29.318076Z","pmid":"40292527","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}