Fish oil supplementation modifies the associations between genetically predicted and observed concentrations of blood lipids: a cross-sectional gene-diet interaction study in UK Biobank

Jul 17, 2024The American journal of clinical nutrition

Fish oil changes how genes relate to blood fat levels in UK Biobank participants

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Abstract

Fish oil supplementation may attenuate the association between genetically predicted and observed concentrations of total cholesterol, LDL cholesterol, and triglycerides in 424,090 participants of European ancestry.

Fish oil is associated with a reduced relationship between genetic predisposition and observed levels of total cholesterol, LDL cholesterol, and triglycerides.
In contrast, fish oil appears to enhance the association between genetic prediction and observed levels of HDL cholesterol.
For triglycerides, each standard deviation increase in genetic predisposition correlates with a 0.254 standard deviation increase in observed concentration among fish oil users.
A stronger association of 0.267 standard deviations was found in nonusers regarding triglyceride levels.
Similar results were observed in African-ancestry participants, indicating that fish oil may significantly alter lipid associations.

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BACKGROUND: Dyslipidemia is a well-known risk factor for cardiovascular disease, the leading cause of mortality worldwide. Although habitual intake of fish oil is associated with cardioprotective effects through triglyceride reduction, the interactions of fish oil with the genetic predisposition to dysregulated lipids remain elusive.

OBJECTIVES: We examined whether fish oil supplementation modifies the association between genetically predicted and observed concentrations of total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides.

METHODS: A total of 441,985 participants with complete genetic and phenotypic data from the UK Biobank were included. Polygenic scores (PGS) of the 4 lipids were calculated in participants of diverse ancestries. For each lipid, multivariable linear regression models were used to assess if fish oil supplementation modified the association between PGS and the observed circulating concentration, with adjustment for relevant covariates.

RESULTS: Fish oil supplementation attenuates the associations between genetically predicted and observed circulating concentrations of total cholesterol, LDL cholesterol, and triglycerides while accentuating the corresponding association for HDL cholesterol among 424,090 participants of European ancestry. Consistent significant findings were obtained using PGS calculated based on multiple genome-wide association studies or alternative PGS methods. For triglycerides, each standard deviation (SD) increment in PGS is associated with 0.254 [95% confidence interval (CI): 0.248, 0.259] SD increase in the observed concentration among European-ancestry participants who reported fish oil usage. In contrast, a stronger association was observed in nonusers (0.267; 95% CI: 0.263, 0.270). Consistently, we showed that fish oil significantly attenuates the association between genetically predicted and observed concentrations of triglycerides in African-ancestry participants.

CONCLUSIONS: Fish oil supplementation attenuates the association between genetically predicted and observed circulating concentrations of total cholesterol, LDL cholesterol, and triglycerides while accentuating the corresponding association for HDL cholesterol in individuals of European ancestry. Further research is needed to understand the clinical implications of these findings.

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Fish oil supplementation modifies the associations between genetically predicted and observed concentrations of blood lipids: a cross-sectional gene-diet interaction study in UK Biobank

Abstract

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