Pathway-Based Genetic Risk Scores Are Associated with Blood Lipids Among Young Mexican Adults

Area of Science:

• Genetics
• Metabolic Diseases
• Population Health

Background:

• Mexicans experience high rates of dyslipidemia, characterized by low HDL-C and high TG.
• Previous genetic studies on dyslipidemia, mainly in European populations, identified SNPs with limited replication.
• Genetic risk scores (GRS) offer a way to assess cumulative SNP effects on lipid variability.

Purpose of the Study:

• To develop a GRS using lipid metabolism SNPs in young Mexican adults.
• To investigate the association between this GRS and blood lipid concentrations (TG and HDL-C).

Main Methods:

• Genotyping of 14 SNPs in lipid metabolism pathways (RCT, cellular uptake, lipoprotein formation).
• Calculation of additive and weighted GRS for pathways and total GRS.
• Analysis of associations between SNPs, GRS, and lipid levels using general linear models.

Main Results:

• Additive RCT and total GRS were linked to triglyceride (TG) levels (p < 0.05), explaining 3.4% and 6.1% of variability, respectively.
• Weighted RCT GRS associated with HDL-C (p = 0.007).
• The ABCA1 rs9282541 variant showed the strongest association with HDL-C (p = 0.016); its removal abolished the GRS-HDL-C association.

Conclusions:

• SNPs in lipoprotein metabolism pathways cumulatively influence lipid concentrations in young Mexican adults.
• The ABCA1-rs9282541 variant is a key determinant of HDL-C levels in this population.
• Further research is needed on genetic admixture and lifestyle factors in Mexican dyslipidemia.