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

Am J Clin Nutr. 2024 Jul 15:S0002-9165(24)00605-1. doi: 10.1016/j.ajcnut.2024.07.009. Online ahead of print.

ABSTRACT

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 levels 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 four 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 level, with adjustment for relevant covariates.

RESULTS: Fish oil supplementation attenuates the associations between genetically predicted and observed circulating levels 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% CI = 0.248 – 0.259) SD increase in the observed level among European-ancestry participants who reported fish oil usage. In contrast, a stronger association was observed in non-users (0.267, 95% CI = 0.263 – 0.270). Consistently, we showed that fish oil significantly attenuates the association between genetically predicted and observed levels of triglycerides in African-ancestry participants.

CONCLUSIONS: Fish oil supplementation attenuates the association between genetically predicted and observed circulating levels 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.

PMID:39019260 | DOI:10.1016/j.ajcnut.2024.07.009