A systematic analysis highlights multiple long non-coding RNAs associated with cardiometabolic disorders

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Title: A systematic analysis highlights multiple long non-coding RNAs associated with cardiometabolic disorders
Author(s): Ghanbari, M
Peters, MJ
De Vries, PS
Boer, CG
Van Rooij, JGJ
Lee, YC
Kumar, V
Uitterlinden, AG
Ikram, MA
Wijmenga, C
Ordovas, JM
Smith, CE
Van Meurs, JBJ
Erkeland, SJ
Franco, OH
Dehghan, A
Item 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.
Publication Date: 30-Jan-2018
Date of Acceptance: 5-Dec-2017
URI: http://hdl.handle.net/10044/1/60610
DOI: https://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
Keywords: 0604 Genetics
1103 Clinical Sciences
Genetics & Heredity
Publication Status: Published
Online Publication Date: 2018-01-30
Appears in Collections:Faculty of Medicine
Epidemiology, Public Health and Primary Care



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