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

Mohsen Ghanbari, Marjolein J Peters, Paul S de Vries, Cindy G Boer, Jeroen G J van Rooij, Yu-Chi Lee, Vinod Kumar, André G Uitterlinden, M Arfan Ikram, Cisca Wijmenga, Jose M Ordovas, Caren E Smith, Joyce B J van Meurs, Stefan J Erkeland, Oscar H Franco, Abbas Dehghan

Research output: Contribution to journalArticleAcademicpeer-review

10 Citations (Scopus)

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 x 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.

Original languageEnglish
Pages (from-to)431-446
Number of pages16
JournalJournal of human genetics
Volume63
Issue number4
Early online date30-Jan-2018
DOIs
Publication statusPublished - Apr-2018

Keywords

  • CORONARY-ARTERY-DISEASE
  • GENOME-WIDE ASSOCIATION
  • TYPE-2 DIABETES SUSCEPTIBILITY
  • FUNCTIONAL ANNOTATION
  • GENETIC ARCHITECTURE
  • GLYCEMIC TRAITS
  • BLOOD-PRESSURE
  • KCNQ1 LOCUS
  • VARIANTS
  • INSULIN

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