A genetic sum score of effect alleles associated with serum lipid concentrations interacts with educational attainment

Carina Emmel,Raimund Erbel,Karl-Heinz Jöckel,Nico Dragano,Markus M Nöthen,Börge Schmidt,Mirjam Frank

doi:10.1038/s41598-021-95970-z

Abstract

High-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and total cholesterol (TC) levels are influenced by both genes and the environment. The aim was to investigate whether education and income as indicators of socioeconomic position (SEP) interact with lipid-increasing genetic effect allele scores (GES) in a population-based cohort. Using baseline data of 4516 study participants, age- and sex-adjusted linear regression models were fitted to investigate associations between GES and lipids stratified by SEP as well as including GES×SEP interaction terms. In the highest education group compared to the lowest stronger effects per GES standard deviation were observed for HDL-C (2.96 mg/dl [95%-CI: 2.19, 3.83] vs. 2.45 mg/dl [95%-CI: 1.12, 3.72]), LDL-C (6.57 mg/dl [95%-CI: 4.73, 8.37] vs. 2.66 mg/dl [95%-CI: −0.50, 5.76]) and TC (8.06 mg/dl [95%-CI: 6.14, 9.98] vs. 4.37 mg/dl [95%-CI: 0.94, 7.80]). Using the highest education group as reference, interaction terms showed indication of GES by low education interaction for LDL-C (ßGES×Education: −3.87; 95%-CI: −7.47, −0.32), which was slightly attenuated after controlling for GESLDL-C×Diabetes interaction (ßGES×Education: −3.42; 95%-CI: −6.98, 0.18). The present study showed stronger genetic effects on LDL-C in higher SEP groups and gave indication for a GESLDL-C×Education interaction, demonstrating the relevance of SEP for the expression of genetic health risks.

Highlights

Elevated serum concentration of low-density lipoprotein cholesterol (LDL-C) is an important causal risk factor for cardiovascular disease (CVD)[1,2,3] and has largely replaced total cholesterol (TC) as the primary treatment target for d yslipidemia[1]
Participants in the lowest education group (≤ 10 years) had a 4.14 (95%-CI: -5.82, −2.47) mg/dl lower high-density lipoprotein cholesterol (HDL-C), a 4.23 (95%-CI: 0.37, 8.09) mg/dl higher LDL-C and 3.34 (95%-CI: −0.81, 7.49) mg/dl higher TC level compared to the participants in the highest education group (≥ 14 years) with similar patterns for income (Table 2)
Results gave some indication for an interaction between the GESLipid and the socioeconomic position (SEP) indicator education, which was strongest for LDL-C

Summary

Introduction

Elevated serum concentration of low-density lipoprotein cholesterol (LDL-C) is an important causal risk factor for cardiovascular disease (CVD)[1,2,3] and has largely replaced total cholesterol (TC) as the primary treatment target for d yslipidemia[1]. Reduced serum concentration of high-density lipoprotein cholesterol (HDL-C) is independently associated with CVD4,5, in genetic studies HDL-C has not been causally associated with CVD3. The genome-wide association study (GWAS) meta-analysis from the Global Lipids Genetics Consortium (GLGC) in 2013 identified 157 loci associated with lipids accounting for up to 12% of the variance in each lipid trait[14]. In contrast family-based association studies have indicated that 30–70% of the variance in lipids is genetically b ased[18,19]. Investigating interactions between lipid-associated loci and SEP indicators may be crucial for identifying subgroups for which genetic effects show stronger signals than for the average p opulation[34] and who may benefit from genotype-based targeted intervention[35]

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Conclusion