Chapter I. Pathogenesis

Get Permission
Rev Diabet Stud, 2012, 9(4):201-223 DOI 10.1900/RDS.2012.9.201

From Markers to Molecular Mechanisms: Type 1 Diabetes in the Post-GWAS Era

Alan G. Baxter, Margaret A. Jordan

Comparative Genomics Centre, Molecular Sciences Building 21, James Cook University, Townsville QLD 4811, Australia
Address correspondence to: Alan G. Baxter, e-mail

Manuscript submitted December 16, 2012; resubmitted February 2, 2013; accepted February 8, 2013.

Keywords: type 1 diabetes, genome-wide association study, GWAS, HLA, Lyp, IDDM, linkage analysis, polymorphism, haplotype


By the year 2000, a draft of the human genome sequence was completed. Millions of single-nucleotide polymorphisms (SNPs) had been deposited into public databases, and high throughput technologies were under development for SNP genotyping. At that time, it was predicted that large case control association studies would provide far better resolution and power than genome-wide linkage studies. Type 1 diabetes was one of the first phenotypes to be examined by genome-wide association studies (GWAS), and to date over 50 genomic regions have been associated with the disease. In general, the great majority of these loci individually contribute a relatively small degree of risk, and most loci lie outside of coding sequences. The identification of molecular mechanisms from these genomic data therefore remains a significant challenge. Here, we summarize genetic candidate, linkage, and association studies of type 1 diabetes and discuss a potential strategy to identify mechanisms of disease from genomic data.

Fulltext: HTML , PDF (1.0 MB)

This article has been cited by other articles:

Association between telomere length and diabetes mellitus: A meta-analysis

Wang J, Dong X, Cao L, Sun Y, Qiu Y, Zhang Y, Cao R, Covasa M, Zhong L

J Int Med Res 2016. 44(6):1156-1173

How Can We Explain Very Low Odds Ratios in GWAS? I. Polygenic Models

Hodge SE, Greenberg DA

Hum Hered 2016. 81(4):173-180

A Bioinformatics Approach to the Identification of Variants Associated with Type 1 and Type 2 Diabetes Mellitus that Reside in Functionally Validated miRNAs Binding Sites

Ghaedi H, Bastami M, Jahani MM, Alipoor B, Tabasinezhad M, Ghaderi O, Nariman-Saleh-Fam Z, Mirfakhraie R, Movafagh A, Omrani MD, Masotti A

Biochem Genet 2016. 54(3):211-221

Genetic variations in the PSMA3, PSMA6 and PSMC6 genes are associated with type 1 diabetes in Latvians and with expression level of number of UPS-related and T1DM-susceptible genes in HapMap individuals

Sjakste T, Paramonova N, Osina K, Dokane K, Sokolovska J, Sjakste N

Mol Genet Genomics 2016. 291(2):891-903