23 September 2020
Researchers identify Greenlandic genetic variant that predisposes to diabetes
Published online 14 July 2014
The prevalence of type-2 diabetes has increased markedly among the Inuit population of Greenland. In an effort to understand the genetic factors that predispose the population to diabetes, a team of scientists used gene chip technology to genotype almost 5% of Greenland’s inhabitants, publishing their findings in Nature.1
They discovered a genetic variant of such pronounced effect that, when inherited from both parents, the risk of diabetes is increased tenfold.
The research team, including Jumana Al-Aama and Jun Wang of King Abdulaziz University, Jeddah, Saudi Arabia, analysed type-2-diabetes-associated traits, such as insulin and glucose levels after eating, and associated them with gene chip data for metabolically linked genetic variation.
The variant they discovered had not previously been linked to diabetes in humans. It causes the production of a truncated and inactive form of the TBC1D4 protein. This protein is necessary for proper glucose transport in muscle cells; in its absence, the muscles become resistant to insulin signalling.
The variant is carried by 23% of the Inuit population and is estimated to account for more than 10% of the cases of type-2 diabetes on the island. Whether this variation emerged as an adaptation in a population whose diet was historically very low in carbohydrates and very high in protein and fat, or due to genetic drift is still unclear.
The successful discovery of a genetic variant of such large effect also demonstrates the power of conducting genetic association studies on isolated and inbred populations.
“We strongly believe that similar studies in other isolated populations could be fruitful,” explains Torben Hansen of the University of Copenhagen, who led the research along with Anders Albrechtsen. “Maybe Middle East populations could be of special interest due to the relatively large degree of inbreeding.”
- Moltke, I. et al. A common Greenlandic TBC1D4 variant confers muscle insulin resistance and type 2 diabetes. Nature doi:10.1038/nature13425 (2014).