Integrating genetics and lifestyles for precision nutrition in hypertriglyceridemia: A UK Biobank and KoGES analysis

Hypertriglyceridemia is an independent risk factor for cardiovascular disease.

This study examined the polygenic variants associated with high serum triglyceride concentration (high-TG) and their interactions with lifestyle factors using data from the UK Biobank (n = 479,300) and the Korean Genome and Epidemiology Study (KoGES; n = 57,939).

High-TG group was categorized based on over 200 mg/dL fasting serum TG concentrations (Caucasians, UK Biobank, n = 100,543; Koreans, KoGES, n = 7211). Polygenic risk scores (PRS) were calculated using risk alleles from genetic variants identified through a genome-wide association study (GWAS) and generalized multifactor dimensionality reduction (GMDR) analyses.

Koreans showed higher frequencies of risk alleles in GCKR, APOA5, SIK3, and APOE genes compared to Caucasians. After adjusting for covariates, a PRS including lipoprotein lipase (LPL)_rs328, apolipoprotein A5 (APOA5)_rs2072560, and glucokinase regulator (GCKR)_rs780093 showed a 2.2-fold (UK Biobank) and 2.6-fold (KoGES) increased risk of high-TG among Caucasians and Koreans, respectively. In both cohorts, the PRS was positively associated with metabolic syndrome, serum low high-density lipoprotein (HDL)-cholesterol, and high low-density lipoprotein (LDL)-cholesterol concentrations, but inversely associated with high-TG. These variants were linked to the chylomicron and very low-density lipoprotein (VLDL) remodeling pathways in Multimarker Analysis of GenoMic Annotation (MAGMA) gene analysis. Significant interactions were observed between the PRS and lifestyle factors, namely plant-based diet (P = .0008), alcohol consumption (P = .0022), and smoking status (P < .001) in both cohorts. Additionally, in the KoGES cohort, vitamin D intake (P = .027) and the glycemic index (P = .045) interacted with the PRS to influence high-TG risk.

Similar genetic variants affected high-TG risk across populations despite ethnic differences in risk allele frequencies. The identified PRS significantly interacted with plant-based diet, alcohol consumption, and smoking status in both cohorts, with additional interactions observed with vitamin D intake and glycemic index in the Korean cohort.