Genes regulating levels of ω-3 long-chain polyunsaturated fatty acids are associated with alcohol use disorder and consumption, and broader externalizing behavior in humans.
Average rating
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Star rating
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Journal title
Alcoholism, clinical and experimental researchDate Published
2022-08-07Publication Volume
46Publication Issue
9Publication Begin page
1657Publication End page
1664
Metadata
Show full item recordAbstract
Background: Individual variation in the physiological response to alcohol is predictive of an individual's likelihood to develop alcohol use disorder (AUD). Evidence from diverse model organisms indicates that the levels of long-chain polyunsaturated omega-3 fatty acids (ω-3 LC-PUFAs) can modulate the behavioral response to ethanol and therefore may impact the propensity to develop AUD. While most ω-3 LC-PUFAs come from diet, humans can produce these fatty acids from shorter chain precursors through a series of enzymatic steps. Natural variation in the genes encoding these enzymes has been shown to affect ω-3 LC-PUFA levels. We hypothesized that variation in these genes could contribute to the susceptibility to develop AUD. Methods: We identified nine genes (FADS1, FADS2, FADS3, ELOVL2, GCKR, ELOVL1, ACOX1, APOE, and PPARA) that are required to generate ω-3 LC-PUFAs and/or have been shown or predicted to affect ω-3 LC-PUFA levels. Using both set-based and gene-based analyses we examined their association with AUD and two AUD-related phenotypes, alcohol consumption, and an externalizing phenotype. Results: We found that the set of nine genes is associated with all three phenotypes. When examined individually, GCKR, FADS2, and ACOX1 showed significant association signals with alcohol consumption. GCKR was significantly associated with AUD. ELOVL1 and APOE were associated with externalizing. Conclusions: Taken together with observations that dietary ω-3 LC-PUFAs can affect ethanol-related phenotypes, this work suggests that these fatty acids provide a link between the environmental and genetic influences on the risk of developing AUD.Citation
Aliev F, Barr PB, Davies AG, Dick DM, Bettinger JC. Genes regulating levels of ω-3 long-chain polyunsaturated fatty acids are associated with alcohol use disorder and consumption, and broader externalizing behavior in humans. Alcohol Clin Exp Res. 2022 Sep;46(9):1657-1664. doi: 10.1111/acer.14916. Epub 2022 Aug 7. PMID: 35904282; PMCID: PMC9509483.DOI
10.1111/acer.14916ae974a485f413a2113503eed53cd6c53
10.1111/acer.14916
Scopus Count
Collections
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as © 2022 The Authors. Alcoholism: Clinical & Experimental Research published by Wiley Periodicals LLC on behalf of Research Society on Alcoholism.
Related articles
- Dietary Omega-3 Fatty Acids Differentially Impact Acute Ethanol-Responsive Behaviors and Ethanol Consumption in DBA/2J Versus C57BL/6J Mice.
- Authors: Wolstenholme JT, Bowers MS, Pais AB, Pais AC, Poland RS, Poklis JL, Davies AG, Bettinger JC
- Issue date: 2018 Aug
- Long-Chain ω-3 Levels Are Associated With Increased Alcohol Sensitivity in a Population-Based Sample of Adolescents.
- Authors: Edwards AC, Heron J, Hibbeln J, Schuckit MA, Webb BT, Hickman M, Davies AG, Bettinger JC
- Issue date: 2019 Dec
- Patterns of perinatal polyunsaturated fatty acid status and associated dietary or candidate-genetic factors.
- Authors: Abou Assi A, Heude B, Plancoulaine S, Sarté C, Tafflet M, Yuan WL, Charles MA, Armand M, Bernard JY
- Issue date: 2024 Jun
- Genetic Variants of the FADS Gene Cluster Are Associated with Erythrocyte Membrane LC PUFA Levels in Patients with Mild Cognitive Impairment.
- Authors: Schuchardt JP, Köbe T, Witte V, Willers J, Gingrich A, Tesky V, Pantel J, Rujescu D, Illig T, Flöel A, Hahn A
- Issue date: 2016
- Genome-Wide Association Study for Serum Omega-3 and Omega-6 Polyunsaturated Fatty Acids: Exploratory Analysis of the Sex-Specific Effects and Dietary Modulation in Mediterranean Subjects with Metabolic Syndrome.
- Authors: Coltell O, Sorlí JV, Asensio EM, Barragán R, González JI, Giménez-Alba IM, Zanón-Moreno V, Estruch R, Ramírez-Sabio JB, Pascual EC, Ortega-Azorín C, Ordovas JM, Corella D
- Issue date: 2020 Jan 24