DNA methylation profiling identifies a high effect genetic variant for lipoprotein(a) levels
Gregory T Jones1, Judith Marsman1, Basharat Bhat1
1Departments of Surgical Sciences, University of Otago , Dunedin, New Zealand.
Epigenetics
|April 3, 2020
Summary
This study found a specific DNA methylation site linked to lipoprotein(a) [Lp(a)] levels. This association is driven by a rare genetic variant, highlighting methylation
Area of Science:
- Genetics
- Epigenetics
- Cardiovascular Disease Research
Background:
- Circulating lipoprotein(a) [Lp(a)] is an independent cardiovascular disease risk factor.
- DNA methylation changes are linked to blood lipid levels.
- Epigenome-wide association studies (EWAS) are valuable for discovering genetic associations.
Purpose of the Study:
- To conduct a discovery and validation EWAS for plasma Lp(a) levels.
- To identify specific CpG sites associated with Lp(a).
- To investigate the genetic underpinnings of Lp(a) methylation associations.
Main Methods:
- Utilized Illumina EPIC and 450k arrays for whole-blood DNA methylation profiling in elderly cohorts.
- Measured plasma Lp(a) using an apolipoprotein(a)-size-independent ELISA.
- Performed epigenome-wide rank regression analysis and SNP genotyping.
Main Results:
- Identified and validated a significant association between cg17028067 (LPA gene intron 1) and plasma Lp(a) levels.
- Discovered that an uncommon SNP (rs76735376) at the CpG site largely explains the methylation effect.
- Rs76735376 acts as an expression quantitative trait loci for the LPA gene, potentially affecting expression via enhancer activity.
Conclusions:
- This EWAS identified a novel CpG site within the LPA gene associated with Lp(a) levels.
- The identified association is primarily driven by a rare, potent genetic variant (rs76735376).
- CpG methylation analysis can reveal genetic associations not easily detected by traditional genetic studies.
Keywords:
DNA methylationlipoprotein(a)methylation quantitative trait locisingle-nucleotide polymorphismMore Related Videos
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