Next Article in Journal
Identifying Bird Remains Using Ancient DNA Barcoding
Next Article in Special Issue
The Genetic Architecture of Type 1 Diabetes
Previous Article in Journal
A Comparative Study of the Structural Dynamics of Four Terminal Uridylyl Transferases
Previous Article in Special Issue
The Clinical Course of Patients with Preschool Manifestation of Type 1 Diabetes Is Independent of the HLA DR-DQ Genotype
Article Menu
Issue 6 (June) cover image

Export Article

Open AccessReview
Genes 2017, 8(6), 167;

Effects of Type 1 Diabetes Risk Alleles on Immune Cell Gene Expression

Centre for Diabetes Research, Harry Perkins Institute of Medical Research, Nedlands, WA 6009, Australia
Centre of Medical Research, University of Western Australia, Nedlands, WA 6009, Australia
Author to whom correspondence should be addressed.
Received: 2 March 2017 / Revised: 17 May 2017 / Accepted: 14 June 2017 / Published: 21 June 2017
(This article belongs to the Special Issue Genetics and Functional Genomics of Diabetes Mellitus)
Full-Text   |   PDF [1245 KB, uploaded 21 June 2017]   |  


Genetic studies have identified 61 variants associated with the risk of developing Type 1 Diabetes (T1D). The functions of most of the non-HLA (Human Leukocyte Antigen) genetic variants remain unknown. We found that only 16 of these risk variants could potentially be linked to a protein-coding change. Therefore, we investigated whether these variants affected susceptibility by regulating changes in gene expression. To do so, we examined whole transcriptome profiles of 600 samples from the Type 1 Diabetes Genetics Consortium (T1DGC). These comprised four different immune cell types (Epstein-Barr virus (EBV)-transformed B cells, either basal or after stimulation; and cluster of differentiation (CD)4+ and CD8+ T cells). Many of the T1D-associated risk variants regulated expression of either neighboring (cis-) or distant (trans-) genes. In brief, 24 of the non-HLA T1D variants affected the expression of 31 nearby genes (cis) while 25 affected 38 distant genes (trans). The effects were highly significant (False Discovery Rate p < 0.001). In addition, we searched in public databases for expression effects of T1D single nucleotide polymorphisms (SNPs) in other immune cell types such as CD14+ monocytes, lipopolysaccharide (LPS) stimulated monocytes, and CD19+ B cells. In this paper, we review the (expression quantitative trait loci (eQTLs) associated with each of the 60 T1D variants and provide a summary of the genes impacted by T1D risk alleles in various immune cells. We then review the methodological steps involved in analyzing the function of genome wide association studies (GWAS)-identified variants, with emphasis on those affecting gene expression. We also discuss recent advancements in the methodologies and their advantages. We conclude by suggesting future study designs that will aid in the study of T1D risk variants. View Full-Text
Keywords: type 1 diabetes; eQTLs; B-cells; T-cells; dendritic cells type 1 diabetes; eQTLs; B-cells; T-cells; dendritic cells

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material


Share & Cite This Article

MDPI and ACS Style

Ram, R.; Morahan, G. Effects of Type 1 Diabetes Risk Alleles on Immune Cell Gene Expression. Genes 2017, 8, 167.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Genes EISSN 2073-4425 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top