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Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
Genome-wide association study identifies common variants associated with circulating vitamin E levels
Jacqueline M Major1, Kai Yu, William Wheeler
1Division of Cancer Epidemiology and Genetics and Core Genotyping Facility, National Cancer Institute, NIH, Bethesda, MD 20892, USA,
Human Molecular Genetics
|July 7, 2011
Summary
Genome-wide association studies identified three genetic loci linked to alpha-tocopherol levels in men. These single-nucleotide polymorphisms (SNPs) are associated with lipid metabolism and explain a small portion of alpha-tocopherol variance.
Area of Science:
- Human Genetics
- Nutritional Genomics
- Metabolomics
Background:
- Circulating concentrations of tocopherols, particularly alpha-tocopherol, are influenced by genetic factors.
- Understanding these genetic influences is crucial for comprehending vitamin E metabolism and its health implications.
Purpose of the Study:
- To identify common genetic variants associated with alpha- and gamma-tocopherol concentrations in adult men using genome-wide association studies (GWAS).
- To replicate and validate identified genetic associations through meta-analysis.
Main Methods:
- Conducted genome-wide association studies (GWAS) in two adult male cohorts (totaling 5006 men of European descent).
- Utilized meta-analysis to combine findings with independent replication samples.
- Analyzed associations between single-nucleotide polymorphisms (SNPs) and log-transformed tocopherol levels.
Main Results:
- Identified three loci associated with alpha-tocopherol levels: rs964184 (11q23.3), rs2108622 (19pter-p13.11), and rs11057830 (12q24.31).
- Replicated these associations in a combined meta-analysis, with strong statistical significance (P < 10(-8)).
- These three SNPs collectively explain 1.7% of the residual variance in alpha-tocopherol levels; no significant associations were found for gamma-tocopherol.
Conclusions:
- Genome-wide association studies successfully identified novel and confirmed known genetic loci influencing alpha-tocopherol concentrations in men.
- The identified SNPs, associated with lipid metabolism, contribute a modest but significant portion to the heritability of alpha-tocopherol levels.
- Further research is needed to elucidate the role of these genetic variants in vitamin E metabolism and health outcomes.
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