Splicing QTL of human adipose-related traits

Sci Rep. 2018 Jan 10;8(1):318. doi: 10.1038/s41598-017-18767-z.

Abstract

Recently, genome-wide association studies (GWAS) have identified 11 loci associated with adipose-related traits across different populations. However, their functional roles still remain largely unknown. In this study, we aimed to explore the splicing regulation of these GWAS signals in a tissue-specific fashion. For adipose-related GWAS signals, we selected six adipose-related tissues (adipose subcutaneous, artery tibial, blood, heart left ventricle, muscle-skeletal, and thyroid) with the sample size greater than 80 for splicing quantitative trait loci (QTL) analysis using GTEx released datasets. We integrated GWAS summary statistics of nine adipose-related traits (an average of 2.6 million SNPs per GWAS), and splicing QTLs from 6 GTEx tissues with an average of 337,900 splicing QTL SNPs, and 684,859 junctions. Our filtering process generated an average of 86,549 SNPs and 162,841 exon-exon links (junctions) for each tissue. A total of seven exon-exon junctions in four genes (AKTIP, DTNBP1, FTO and UBE2E1) were found to be significantly associated with four SNPs that showed genome-wide significance with body fat distribution (rs17817288, rs7206790, rs11710420 and rs2237199). These splicing events might contribute to the causal effect on the regulation of ectopic-fat, which warrants further experimental validation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adipose Tissue / metabolism
  • Adiposity / genetics*
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO / genetics
  • Apoptosis Regulatory Proteins / genetics
  • Arteries / metabolism
  • Dysbindin / genetics
  • Humans
  • Muscle, Skeletal / metabolism
  • Myocardium / metabolism
  • Polymorphism, Single Nucleotide
  • Quantitative Trait Loci*
  • RNA Splicing*
  • Thyroid Gland / metabolism
  • Ubiquitin-Conjugating Enzymes / genetics

Substances

  • AKTIP protein, human
  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • DTNBP1 protein, human
  • Dysbindin
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • FTO protein, human
  • UBE2E1 protein, human
  • Ubiquitin-Conjugating Enzymes