Abstract P113: Lipid-related Genetic Variants and Lipid Outcomes in a Cohort of Chilean Children

Abstract

Dyslipidemia is an important risk factor for chronic cardiometabolic diseases. Lipid traits are highly heritable and there are currently >185 established loci influencing lipid levels in adults. Recent studies have confirmed that variants associated with lipids influence lipid levels across the lifecourse, and in ancestrally diverse populations. Given that Hispanic/Latinos (HL) shoulder much of the cardiometabolic burden in the United States, it is important to identify genetic variants that contribute the greatest risk for elevated lipid levels across life stages. Thus, our primary aim is to examine the association of known lipid variants with lipid traits identified in large study of adult participants from a Chilean infancy cohort of primarily European-descent. The sample assessed from 2008 to 2013 (n=546) had genotyping and well-measured lipid phenotypes (median age: 16.8 years, interquartile range: 16.6, 16.9). We assessed single variant associations using linear regression for high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and triglycerides (TG), assuming an additive genetic model, adjusted for sex. Additionally, we regressed phenotypes onto weighted trait-specific polygenic risk scores (PRS). Only six variants from the Chilean sample met the a priori threshold of power > 0.8. We found statistically significant effect sizes (mmol/l (se)) for four of the six variants: rs3764261 (0.16 (0.04)) and rs1532085 (0.05 (0.04)) for HDL and rs1260326 (0.34 (0.15)) and rs964184 (0.33 (0.15)) for TG. For each significant variant, direction of effect matched the multiethnic adult GWAS from which SNPs were selected. We compared our findings to a previous study in Finnish children at age 18 years (n=1,216) and found an opposite direction of effect for our significant HDL variants. Likewise, when comparing coefficients for the PRS between the Chilean and Finnish youth sample we found the association to be stronger in the Chilean sample for every trait and gender group with the exception of LDL for males. The lipid loci explained the least amount of total variance for LDL (males=4% and females=5%) and the most amount of variance for HDL (males=20% and females=14%). In conclusion, there is evidence that lipid loci from a HL sample of adolescents contain similar associations as those from European children and adults. Despite the small sample size and possibility for bias with different ancestral groups we found meaningful and statistically significant associations relating lipid loci in a HL cohort of Chilean adolescents with those found in European ancestral groups. These associations emphasize the importance of adolescence as a time for disease prevention given studies demonstrating both the persistence of associations between PRS and lipids over the life course and the increasing role PRS plays in predicting disease.