Genetic regulation of fatty acid content in adipose tissue.
| Title: | Genetic regulation of fatty acid content in adipose tissue. |
|---|---|
| Authors: | Yan X; Department of Twin Research and Genetic Epidemiology, King's College London, SE1 7EH London, UK.; Roberts AL; Department of Twin Research and Genetic Epidemiology, King's College London, SE1 7EH London, UK.; El-Sayed Moustafa JS; Department of Twin Research and Genetic Epidemiology, King's College London, SE1 7EH London, UK.; Villicaña S; Department of Twin Research and Genetic Epidemiology, King's College London, SE1 7EH London, UK.; Al-Hilal M; Department of Nutritional Sciences, King's College London, SE1 9NH London, UK; Health and Vital Statistics Division, National Center for Health Information, Ministry of Health, Sulaibkhat 13001, Kuwait.; Tomlinson M; Department of Twin Research and Genetic Epidemiology, King's College London, SE1 7EH London, UK; Department of Medical and Molecular Genetics, King's College London, SE1 9RT London, UK.; Menni C; Department of Twin Research and Genetic Epidemiology, King's College London, SE1 7EH London, UK; Department of Pathophysiology and Transplantation, Università Degli Studi di Milano, 20122 Milan, Italy; Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, 20122 Milan, Italy.; Sanders TAB; Department of Nutritional Sciences, King's College London, SE1 9NH London, UK.; Freidin MB; Department of Twin Research and Genetic Epidemiology, King's College London, SE1 7EH London, UK.; Bell JT; Department of Twin Research and Genetic Epidemiology, King's College London, SE1 7EH London, UK.; Small KS; Department of Twin Research and Genetic Epidemiology, King's College London, SE1 7EH London, UK. Electronic address: kerrin.small@kcl.ac.uk. |
| Source: | American journal of human genetics [Am J Hum Genet] 2026 Feb 05; Vol. 113 (2), pp. 291-308. Date of Electronic Publication: 2026 Jan 14. |
| Publication Type: | Journal Article; Twin Study |
| Language: | English |
| Journal Info: | Publisher: Cell Press Country of Publication: United States NLM ID: 0370475 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1537-6605 (Electronic) Linking ISSN: 00029297 NLM ISO Abbreviation: Am J Hum Genet Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2008- : [Cambridge, MA] : Cell Press; Original Publication: Baltimore, American Society of Human Genetics. |
| MeSH Terms: | Fatty Acids*/metabolism ; Fatty Acids*/genetics ; Adipose Tissue*/metabolism ; Gene Expression Regulation*; Quantitative Trait Loci/genetics ; DNA Methylation/genetics ; Humans ; Female ; Genome-Wide Association Study ; Middle Aged ; Aged ; Adult ; Multifactorial Inheritance ; Polymorphism, Single Nucleotide |
| Abstract: | Fatty acids are important as structural components, energy sources, and signaling mediators. While studies have extensively explored genetic regulation of fatty acids in serum and other bodily fluids, their regulation within adipose tissue, a crucial regulator of cardiovascular and metabolic health, remains unclear. Here, we investigated the genetic regulation of 18 fatty acids in subcutaneous adipose tissue from 569 female twins from TwinsUK. Using twin models, the heritability of fatty acids ranged from 5% to 59%, indicating a substantial genetic regulation of fatty acid levels within adipose tissue, which was also tissue specific in many cases. Genome-wide association studies identified 10 significant loci, in SCD, ADAMTSL1, ZBTB41, SNTB1, EXOC6B, ACSL3, LINC02055, MKRN2/TSEN2, FADS1, and HAPLN across 13 fatty acids or fatty acid product-to-precursor ratios. Using adipose gene expression and methylation, which were concurrently measured in these samples, we detected five fatty acid-associated signals that colocalized with expression quantitative trait locus (eQTL) and methylation quantitative trait locus (meQTL) signals, highlighting fatty acids that are regulated by molecular processes within adipose tissue. We explored links between polygenic scores of common metabolic traits and adipose fatty acid levels and identified associations between polygenic scores of BMI, body-fat distribution, and triglycerides and several fatty acids, indicating these risk scores impact local adipose tissue content. Overall, our results identified local genetic regulation of fatty acids within adipose tissue and highlighted their links with renal and cardio-metabolic health.; (Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.) |
| Competing Interests: | Declaration of interests The authors declare no competing interests. |
| Contributed Indexing: | Keywords: adipose tissue; fatty acid; genome-wide association study; polygenic score |
| Substance Nomenclature: | 0 (Fatty Acids) |
| Entry Date(s): | Date Created: 20260114 Date Completed: 20260206 Latest Revision: 20260512 |
| Update Code: | 20260513 |
| PubMed Central ID: | PMC13087407 |
| DOI: | 10.1016/j.ajhg.2025.12.008 |
| PMID: | 41534528 |
| Database: | MEDLINE |
Journal Article; Twin Study