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Gene-educational attainment interactions in a multi-population genome-wide meta-analysis identify novel lipid loci
Lisa de las Fuentes1,2, Karen L Schwander2,3, Michael R Brown4
1Cardiovascular Division, Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States.
Frontiers in Genetics
|November 29, 2023
Summary
This study identified 18 new genetic regions influencing cholesterol and triglyceride levels, with four showing a link between genes and educational attainment. These findings highlight potential new drug targets for lipid metabolism disorders.
Area of Science:
- Genetics
- Epidemiology
- Cardiovascular Health
Background:
- Educational attainment is a key predictor of cardiovascular health and a proxy for socioeconomic status.
- Lipid levels (LDL, HDL, TG) are crucial cardiovascular risk factors.
- Understanding genetic influences on lipid levels, especially in relation to socioeconomic factors, is vital for public health.
Purpose of the Study:
- To conduct a genome-wide meta-analysis of lipid levels (LDL, HDL, TG) accounting for gene-educational attainment interactions.
- To identify novel genetic loci associated with lipid levels and their interaction with educational attainment.
- To explore the biological relevance and potential druggability of identified genes.
Main Methods:
- A two-stage genome-wide meta-analysis involving up to 226,315 individuals.
- Analysis of two educational attainment variables: 'Some College' and 'Graduated College'.
- Genome-wide association analysis for significant and suggestive variants, followed by Stage 2 replication.
Main Results:
- Identified 18 novel lipid loci (9 for LDL, 7 for HDL, 2 for TG) through joint tests of main and interaction effects.
- Four loci demonstrated significant interaction with educational attainment.
- Several identified genes have roles in adipose, brain, and liver biology, suggesting complex regulatory pathways.
Conclusions:
- Genome-wide interaction analysis with educational attainment reveals novel lipid loci missed by traditional methods.
- Identified genes involved in brain-adipose-liver communication may be important for lipid metabolism regulation.
- Five gene targets show potential druggability with FDA-approved drugs, offering therapeutic avenues.
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