Key result
Higher lipid genetic risk score independently linked to ~29% greater odds of hypertriglyceridemia.
Why the study?
Understanding the genetic and environmental basis of hypertriglyceridemia could open new translational opportunities in clinical decisions that are not always consensual.
Are higher genetic risk scores and adverse lifestyle factors independently associated with hypertriglyceridemia in a Portuguese population?
Cohort (n=3,157)
Are higher genetic risk scores and adverse lifestyle factors independently associated with hypertriglyceridemia in a Portuguese population?
Both genetic susceptibility and modifiable lifestyle factors independently contribute to hypertriglyceridemia, emphasizing the role of lifestyle modification in risk reduction.
Answers are grounded in this paper and cite their sources.
Genetic and lifestyle factors independently associated with hypertriglyceridemia; extends prior associations but leaves causal inference and practice change open.
Introduction Hypertriglyceridemia (HTG) is considered a risk factor for atherosclerosis and may sometimes be a monogenic condition. However, in most patients, this is due to the cumulative effect of multiple genetic risk variants along with lifestyle factors, medications, and disease conditions. Understanding the genetic and environmental basis of HTG could open new translational opportunities in clinical decisions that are not always consensual. Objective Investigate the main risk factors, lifestyle and genetics for hypertriglyceridemia during an extensive follow-up in a Portuguese population. Methods A prospective study was conducted on 3,157 enrolled participants from our Research Center dataset, and they were grouped into two categories based on the triglyceride levels below or above 150 mg/dl in admission. An additive genetic risk score (GRS) was constructed using the variants from the lipidic axis and stratified into terciles. A non-parametric Spearman test evaluated the correlation between triglycerides and continuous GRS. The Kruskal-Wallis test investigated triglycerides median differences in the GRS terciles. Multivariate logistic regression entering GRS and adjusted to all confounders (CAD family history, sedentary lifestyle, alcohol abuse, smoking, type 2 diabetes, hypertension and body mass index BMI≥30kg/m2) investigated variables independently associated with high triglyceride levels. Results A Spearman correlation between triglyceride levels and continuous GRS was positive and highly significant (p<0.0001). Median triglyceride levels of 126 mg/dL, 132 mg/dL and 133 mg/dL were obtained for the GRS 1st, 2nd and 3rd terciles, respectively (p<0.0001). After multivariate regression, entering additive GRS adjusted for all confounder variables, the 2ndtercile of GRS presented an OR of high triglycerides of 1.29 (p=0.005) and 3rdtercile an OR of 1.23 (p=0.028), as well as sedentary lifestyle (p=0.001), alcohol abuse (p=0.005), smoking (p<0.0001), diabetes (p<0.0001), hypertension (p<0.0001) and BMI≥30 (p=0.020). Conclusion In our population, genetic loci identified in GWAS and gathered in a lipidic GRS influenced the high triglyceride levels as well as some clinical conditions (diabetes, hypertension and obesity) and lifestyle, such as sedentarism, alcohol abuse, and smoking. A healthy lifestyle, with weight loss without smoking and alcohol and appropriate medication, could protect against genetic susceptibility in reducing triglyceride levels.
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Ferreira et al. (2025) conducted a cohort in Hypertriglyceridemia (n=3,157). Additive genetic risk score (GRS) for lipidic axis vs. 1st tercile of GRS was evaluated on High triglyceride levels (≥150 mg/dl) (OR 1.29, p=0.005).
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