Format

Send to

Choose Destination
Obesity (Silver Spring). 2018 Mar;26(3):559-569. doi: 10.1002/oby.22113. Epub 2018 Jan 29.

Transcriptional Regulatory Mechanisms in Adipose and Muscle Tissue Associated with Composite Glucometabolic Phenotypes.

Author information

1
Department of Biostatistical Sciences, Division of Public Health Sciences, School of Medicine, Wake Forest University, Winston-Salem, North Carolina, USA.
2
Department of Internal Medicine, School of Medicine, Wake Forest University, Winston-Salem, North Carolina, USA.
3
Department of Biochemistry, School of Medicine, Wake Forest University, Winston-Salem, North Carolina, USA.

Abstract

OBJECTIVE:

Tissue-specific gene expression is associated with individual metabolic measures. However, these measures may not reflect the true but latent underlying biological phenotype. This study reports gene expression associations with multidimensional glucometabolic characterizations of obesity, glucose homeostasis, and lipid traits.

METHODS:

Factor analysis was computed by using orthogonal rotation to construct composite phenotypes (CPs) from 23 traits in 256 African Americans without diabetes. Genome-wide transcript expression data from adipose and muscle were tested for association with CPs, and expression quantitative trait loci (eQTLs) were identified by associations between cis-acting single-nucleotide polymorphisms (SNPs) and gene expression.

RESULTS:

The factor analysis identified six CPs. CPs 1 through 6 individually explained 34%, 12%, 9%, 8%, 6%, and 5% of the variation in 23 glucometabolic traits studied. There were 3,994 and 929 CP-associated transcripts identified in adipose and muscle tissue, respectively; CP2 had the largest number of associated transcripts. Pathway analysis identified multiple canonical pathways from the CP-associated transcripts. In adipose and muscle, significant cis-eQTLs were identified for 558 and 164 CP-associated transcripts (q-value < 0.01), respectively.

CONCLUSIONS:

Adipose and muscle transcripts comprehensively define pathways involved in regulating glucometabolic disorders. Cis-eQTLs for CP-associated genes may act as primary causal determinants of glucometabolic phenotypes by regulating transcription of key genes.

PMID:
29377571
PMCID:
PMC5821540
DOI:
10.1002/oby.22113
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center