Chapter I. Pathogenesis and Function

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Rev Diabet Stud, 2015, 12(3-4):320-329 DOI 10.1900/RDS.2015.12.320

Diabetes in Population Isolates: Lessons from Greenland

Niels Grarup1, Ida Moltke2, Anders Albrechtsen2, Torben Hansen1

1Section for Metabolic Genetics, The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
2The Bioinformatics Centre, Department of Biology, University of Copenhagen, 2200 Copenhagen, Denmark
Address correspondence to: Torben Hansen, The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 1, 2100 Copenhagen, Denmark, e-mail:

Manuscript submitted June 22, 2015; resubmitted September 27, 2015; accepted October 16, 2015.

Keywords: type 2 diabetes, population isolate, linkage disequilibrium, GWAS, genetic drift, loss of function


Type 2 diabetes (T2D) is an increasing health problem worldwide with particularly high occurrence in specific subpopulations and ancestry groups. The high prevalence of T2D is caused both by changes in lifestyle and genetic predisposition. A large number of studies have sought to identify the genetic determinants of T2D in large, open populations such as Europeans and Asians. However, studies of T2D in population isolates are gaining attention as they provide several advantages over open populations in genetic disease studies, including increased linkage disequilibrium, homogeneous environmental exposure, and increased allele frequency. We recently performed a study in the small, historically isolated Greenlandic population, in which the prevalence of T2D has increased to more than 10%. In this study, we identified a common nonsense variant in TBC1D4, which has a population-wide impact on glucose-stimulated plasma glucose, serum insulin levels, and T2D. The variant defines a specific subtype of non-autoimmune diabetes characterized by decreased post-prandial glucose uptake and muscular insulin resistance. These and other recent findings in population isolates illustrate the value of performing medical genetic studies in genetically isolated populations. In this review, we describe some of the advantages of performing genetic studies of T2D and related cardio-metabolic traits in a population isolate like the Greenlandic, and we discuss potentials and perspectives for future research into T2D in this population.

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