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  4. A systematic analysis highlights multiple long non-coding RNAs associated with cardiometabolic disorders
 
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A systematic analysis highlights multiple long non-coding RNAs associated with cardiometabolic disorders
File(s)
Revision_ Track Changes accepted.docx (557.17 KB)
Accepted version
Author(s)
Ghanbari, M
Peters, MJ
De Vries, PS
Boer, CG
Van Rooij, JGJ
more
Type
Journal Article
Abstract
Genome-wide association studies (GWAS) have identified many susceptibility loci for cardiometabolic disorders. Most of the associated variants reside in non-coding regions of the genome including long non-coding RNAs (lncRNAs), which are thought to play critical roles in diverse biological processes. Here, we leveraged data from the available GWAS meta-analyses on lipid and obesity-related traits, blood pressure, type 2 diabetes, and coronary artery disease and identified 179 associated single-nucleotide polymorphisms (SNPs) in 102 lncRNAs (p-value < 2.3 × 10-7). Of these, 55 SNPs, either the lead SNP or in strong linkage disequilibrium with the lead SNP in the related loci, were selected for further investigations. Our in silico predictions and functional annotations of the SNPs as well as expression and DNA methylation analysis of their lncRNAs demonstrated several lncRNAs that fulfilled predefined criteria for being potential functional targets. In particular, we found evidence suggesting that LOC157273 (at 8p23.1) is involved in regulating serum lipid-cholesterol. Our results showed that rs4841132 in the second exon and cg17371580 in the promoter region of LOC157273 are associated with lipids; the lncRNA is expressed in liver and associates with the expression of its nearby coding gene, PPP1R3B. Collectively, we highlight a number of loci associated with cardiometabolic disorders for which the association may act through lncRNAs.
Date Issued
2018-01-30
Date Acceptance
2017-12-05
Citation
Journal of Human Genetics, 2018, 63 (4), pp.431-446
URI
http://hdl.handle.net/10044/1/60610
DOI
https://www.dx.doi.org/10.1038/s10038-017-0403-x
ISSN
1434-5161
Publisher
Nature Publishing Group
Start Page
431
End Page
446
Journal / Book Title
Journal of Human Genetics
Volume
63
Issue
4
Copyright Statement
© 2018 The Japan Society of Human Genetics
Subjects
0604 Genetics
1103 Clinical Sciences
Genetics & Heredity
Publication Status
Published
Date Publish Online
2018-01-30
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