Abstract
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.