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A systematic analysis highlights multiple long non-coding RNAs associated with cardiometabolic disorders.
Mohsen Ghanbari1,2, Marjolein J Peters3, Paul S de Vries4
1Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands. m.ghanbari@erasmusmc.nl.
Journal of Human Genetics
|February 1, 2018
Summary
Genome-wide association studies reveal long non-coding RNAs (lncRNAs) linked to cardiometabolic disorders. One lncRNA, LOC157273, shows potential in regulating serum lipids, highlighting lncRNAs as key players in these conditions.
Area of Science:
- Genetics
- Molecular Biology
- Cardiovascular Research
Background:
- Genome-wide association studies (GWAS) have identified numerous genetic loci associated with cardiometabolic disorders.
- A significant proportion of these associated variants are located in non-coding genomic regions, including long non-coding RNAs (lncRNAs).
- lncRNAs are increasingly recognized for their crucial roles in various biological processes.
Purpose of the Study:
- To identify and functionally annotate lncRNAs associated with cardiometabolic disorders using GWAS data.
- To investigate the potential role of specific lncRNAs, such as LOC157273, in regulating metabolic traits.
Main Methods:
- Leveraged GWAS meta-analyses data for lipid, obesity, blood pressure, type 2 diabetes, and coronary artery disease.
- Identified single-nucleotide polymorphisms (SNPs) associated with lncRNAs.
- Performed in silico predictions, functional annotations, expression analysis, and DNA methylation analysis.
Main Results:
- Identified 179 SNPs in 102 lncRNAs associated with cardiometabolic traits (p < 2.3 × 10-7).
- Selected 55 SNPs for further investigation based on linkage disequilibrium.
- Provided evidence for LOC157273 (rs4841132, cg17371580) regulating serum lipid-cholesterol, with expression in the liver and association with PPP1R3B gene expression.
Conclusions:
- Highlights multiple lncRNA loci associated with cardiometabolic disorders.
- Suggests that the effects of these loci on cardiometabolic health may be mediated through lncRNAs.
- Identifies LOC157273 as a potential functional lncRNA target involved in lipid regulation.
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