Transcriptomics in type 2 diabetes: Bridging the gap between genotype and phenotype.
Type 2 diabetes (T2D) is a common, multifactorial disease that is influenced by genetic and environmental factors and their interactions. However, common variants identified by genome wide association studies (GWAS) explain only about 10% of the total trait variance for T2D and less than 5% of the variance for obesity, indicating that a large proportion of heritability is still unexplained. The transcriptomic approach described here uses quantitative gene expression and disease-related physiological data (deep phenotyping) to measure the direct correlation between the expression of specific genes and physiological traits. Transcriptomic analysis bridges the gulf between GWAS and physiological studies. Recent GWAS studies have utilized very large population samples, numbering in the tens of thousands (or even hundreds of thousands) of individuals, yet establishing causal functional relationships between strongly associated genetic variants and disease remains elusive. In light of the findings described below, it is appropriate to consider how and why transcriptomic approaches in small samples might be capable of identifying complex disease-related genes which are not apparent using GWAS in large samples.
South Texas Diabetes and Obesity Institute (STDOI), University of Texas Rio Grande Valley (UTRGV), TX, USA.
Christopher P
CP
Jenkinson
South Texas Diabetes and Obesity Institute (STDOI), University of Texas Rio Grande Valley (UTRGV), TX, USA.
Harald H H
HH
Göring
South Texas Diabetes and Obesity Institute (STDOI), University of Texas Rio Grande Valley (UTRGV), TX, USA.
Rector
R
Arya
South Texas Diabetes and Obesity Institute (STDOI), University of Texas Rio Grande Valley (UTRGV), TX, USA.
John
J
Blangero
South Texas Diabetes and Obesity Institute (STDOI), University of Texas Rio Grande Valley (UTRGV), TX, USA.
Ravindranath
R
Duggirala
Division of Diabetes, Department of Medicine, University of Texas Health Science Center at San Antonio, TX, USA; South Texas Veterans Health Care System, San Antonio, TX, USA.
Ralph A
RA
DeFronzo
ADH1B; GWAS; Gene expression; Insulin resistance; Mexican Americans; Obesity; Transcriptomics; Type 2 diabetes; VAGES; eQTL