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.

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.

Fish oil supplementation modifies the genetic potential for blood lipids.

Background: Dyslipidemia is a well-known risk factor for cardiovascular disease, which has been the leading cause of mortality worldwide. Although habitual intake of fish oil has been implicated in offering 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 can modify the genetic potential for the circulating levels of four lipids, including total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides. Methods: A total of 441,985 participants with complete genetic and phenotypic data from the UK Biobank were included in our study. Polygenic scores (PGS) were calculated in participants of diverse ancestries. Multivariable linear regression models were used to assess associations with adjustment for relevant risk factors. Results: Fish oil supplementation mitigated genetic susceptibility to elevated levels of total cholesterol, LDL-C, and triglycerides, while amplifying genetic potential for increased HDL-C among 424,090 participants of European ancestry Pinteraction<0.05. Consistent significant findings were obtained using PGS calculated based on multiple genome-wide association studies or alternative PGS methods. We also showed that fish oil significantly attenuated genetic predisposition to high triglycerides in African-ancestry participants. Conclusions: Fish oil supplementation attenuated the genetic susceptibility to elevated blood levels of total cholesterol, LDL-C, and triglycerides, while accentuating genetic potential for higher HDL-C. These results suggest that fish oil may have a beneficial impact on modifying genome-wide genetic effects on elevated lipid levels in the general population.