| Title: | Integrating genetics and lifestyles for precision nutrition in hypertriglyceridemia: A UK Biobank and KoGES analysis |
| Journal: | Journal of Clinical Lipidology |
| Published: | 8 May 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40517091/ |
| DOI: | https://doi.org/10.1016/j.jacl.2025.04.202 |
Publication 15393
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Abstract
BACKGROUND: Hypertriglyceridemia is an independent risk factor for cardiovascular disease.</p>
OBJECTIVE: 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).</p>
METHODS: 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.</p>
RESULTS: 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.</p>
CONCLUSION: 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.</p>
15 Keywords
- Adult
- Aged
- Biological Specimen Banks
- Female
- Genome-Wide Association Study
- Humans
- Hypertriglyceridemia
- Life Style
- Male
- Middle Aged
- Polymorphism, Single Nucleotide
- Precision Medicine
- Triglycerides
- UK Biobank
- United Kingdom
6 Authors
- Haeng Jeon Hur
- Hye Jeong Yang
- Min Jung Kim
- Hyun-Jun Jang
- Myung-Sunny Kim
- Sunmin Park
Enabling scientific discoveries that improve human health