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Genome Center’s innovative risk score predicts diabetes more accurately than its predecessors

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“We can see from the data base of the Estonian Genome Center that in Estonia, as well as other parts of the world, type two diabetes is an extremely prevalent disease among middle aged and elderly people—by the age of 60 more than every tenth Estonian lives with this condition,” said Statistician of the Genome Center and UT doctoral student of Mathematical Statistics Kristi Läll.

“People who have type 2 diabetes have a high risk of losing work ability already before retirement age mainly due to the complications of the disease. Complications in the late stages often include impaired kidney function, vision impairment and damage to peripheral blood vessels which could lead to, for example, limb amputation. Premature death occurs two to three times more often among people with diabetes than the rest of the population,” added Senior Research Fellow of the Genome Center Krista Fischer.

“Traditional epidemiological research has shown that one of the most significant risk factors for developing type 2 diabetes is excessive weight. However, not all overweight people have diabetes. And there are also normal weight people who have type 2 diabetes. Developing diabetes depends on the mutual effect of numerous different factors, including genetic background. The percentage of genetic predisposition among the factors which lead to diabetes is nearly 50. Recently, much attention has been given to the possibilities of evaluating the genetic risk,” explained Läll and Fischer.

Together with other researchers of the Genome Center they developed a T2D risk score which is more efficient than before and published it in Genetics in Medicine, an affiliated journal of Nature (http://www.nature.com/gim/journal/vaop/ncurrent/full/gim2016103a.html).

SNPs help identify the risk

Researchers used more than 7,500 different DNA sequences, i.e. SNPs (single-nucleotide polymorphisms), to develop the innovative and more exact method to compute the diabetes risk score.

Researchers have information about millions of SNPs mainly thanks to numerous genome-wide association studies published in the last decade. Although often the effect of individual SNPs on diseases is relatively weak and their cell-biological mechanisms are not completely clear, they can still be used to estimate the risk of developing a disease.

The 7,500 SNPs which the researchers of the Estonian Genome Center considered in the recent study on diabetes risk score were selected on the basis of results in previously published research articles. Using this many gene variants to develop the risk score is new and differs from using a few or few dozen SNPs as has been done previously, said Kristi Läll. “For example, the last study on risk score published before our work estimated the risk of diabetes on the basis of 65 SNPs.”

“As the effect of individual SNPs on developing diabetes is really small, we combine them into one risk score , i.e. one quantitative parameter that estimates  the risk of developing type two diabetes which enables to assess genetic risk better than it has been possible so far,” said Läll.

Research revealed the combined effect of body weight and genetic risk

“We saw, for example, that among overweight but not seriously obese people over the age of 40 (with a body mass index of 25–30), on average five or six percent had diabetes. If high genetic risk (risk score in the top quintile) was added to excessive weight, the risk of developing T2D increased to ten percent.

Meanwhile, only three percent of people with a low genetic risk (but still overweight) developed T2D. This means that people with a higher genetic risk are over three times more likely to develop T2D than people with a low genetic risk,” said Läll.

The doctoral student explained that because being overweight is a risk factor for diabetes, the onset of diabetes is most probable among those people who have a high genetic risk and are overweight. “It means that if you have a high genetic risk of type 2 diabetes, you might develop the disease at an earlier age or with less overweight. But if you are overweight and have a low genetic risk, you might not get diabetes. It must definitely be stressed that low genetic risk does not rule out developing the disease.”

“If a patient is told that they have a high genetic risk, that they are in greater danger and they should therefore be especially attentive about their lifestyle and weight to postpone or avoid diabetes, it might motivate them to monitor their eating habits, physical activity and through this their body weight more closely.”

The study used the data of more than 10,000 Estonian gene donors. In total, the Estonian Genome Center has determined the entire genome sequence of nearly 2,500 gene donors. As a result, counselling is provided to the first gene donors as a pilot project. At first feedback has not been given about the genetic risks of T2D but, for example, concerning hereditary hypercholesterolemia which is characterized by the high blood level of the so called bad cholesterol LDL.

Original article published by University of Tartu

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