'Hope for new treatments' after diabetes genes 'breakthrough'

“Scientists have discovered a clutch of genes that dramatically increase the risk of developing diabetes,” reports the Daily Express. They say the breakthrough “could help develop simple and cheap drugs to tackle the life-threatening illness”.

This story is based on a study that pooled data from studies comparing the DNA of almost 35,000 people with type 2 diabetes and 115,000 people without the disease.

The researchers found 10 new common genetic variations that are associated with an increase of between 7 and 13% in a person’s odds of developing the disease. These studies looked whether specific single “letter” differences (genetic variations) in the DNA code occurred more often in people with type 2 diabetes than those without the disease.

Researchers identified various genes that could be responsible for affecting type 2 diabetes risk, but more research will be needed to confirm that these are definitely involved.

Both genetic and environmental factors (such as diet and physical activity) contribute to a person’s risk of developing type 2 diabetes. These findings bring the total known genetic variations associated with type 2 diabetes to more than 60. This large number of common variations suggests that each contributes only a modest amount to a person’s chance of developing the disease.

It is hoped that having a greater understanding of how type 2 diabetes develops may help in the development of new treatments. Much more research will be needed to determine if this will become a reality.

 

Where did the story come from?

The study was carried out by international researchers belonging to the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium. The study was funded by a large number of government, research and charity organisations, including Diabetes UK.

The study was published in the peer-reviewed Nature Genetics journal.

The Express coverage of the study was not strictly accurate. They suggest that the study has identified “a clutch of genes that dramatically increase the risk of developing diabetes”. This is not correct. The researchers only identified specific areas of DNA associated with type 2 diabetes and have not yet confirmed which genes in these areas are responsible.

Also, these variants each only had a “modest” effect in risk of type 2 diabetes and, together with the known associated variants, they were only estimated to account for just under 6% of the variability in risk of type 2 diabetes in the population. This is far less “dramatic” than implied.

The paper’s claim that the research “could help develop simple and cheap drugs to tackle the life-threatening illness” is also speculation at this time. This is both an important and impressive piece of research. But it is far too early to know whether the work will lead to new innovations in drug research, or whether they will be “simple” or “cheap”.

 

What kind of research was this?

This was a statistical pooling (meta-analysis) of data from case control studies which aimed to identify genetic variations associated with type 2 diabetes. Both genetic and environmental factors contribute to a person’s risk of developing type 2 diabetes. Currently, genetic variations in 56 different areas are known to be associated with risk of type 2 diabetes. However, these are thought only to account for about 10% of the genetic component of risk for type 2 diabetes. The current study aimed to identify more genetic variations associated with risk of type 2 diabetes, and to look at whether looking at all the genetic variations associated with type 2 diabetes could suggest something about how the disease comes about.

Pooling large amounts of data in this way helps researchers identify the influence of genetic variations which separately only contribute a small amount the risk of developing the disease.  It also allows them to estimate how much of the variation in susceptibility to disease is accounted for by the identified “genetic factors” as a whole.

 

What did the research involve?

The researchers initially pooled data from 12 case control studies including 12,171 people with type 2 diabetes (T2D cases) and 56,862 people without the disease (controls). These individuals were of European descent. They also pooled these data with results from 26 studies in 22,669 cases and 58,119 controls, who were mainly of European descent. In total, this meant they had data for 34,840 cases and 114,981 controls.

The researchers looked at data on 196,725 single-letter genetic variations spread throughout the DNA. This included genetic variants that had previously been found to be associated with T2D or related conditions. They were looking for genetic variations in the DNA that were more common in people with T2D than those without the disease. Variations that are more common in people with T2D may be contributing to causing the disease, or may lie near to other genetic variations that are contributing.

 

What were the basic results?

The researchers initially found variations associated with T2D in eight areas of DNA not previously known to be associated with the disease. They also found variations associated with T2D in two areas of DNA not previously known to be associated with the disease in European populations. These variations were common in the population, being carried by between 8 and 89% of chromosomes. They were individually associated with an increase of between 7 and 13% in the odds of having T2D.

Two variations showed different effects in men and women, with one having a greater effect in men and the other having a greater effect in women.

Altogether, these 10 new variations, along with 53 already known areas of DNA linked to T2D were estimated to account for 5.7% of the variability in people’s susceptibility to T2D. The researchers estimated that a further 488 genetic variations showing weaker association with type 2 diabetes could be involved, but larger samples would be needed to confirm this.

The 10 associated variations were near to various genes that could be contributing to the risk of T2D. Looking at these and the genes near to the known variants together, the researchers found that they suggested various biochemical pathways that could be involved in how T2D develops.

 

How did the researchers interpret the results?

The researchers concluded that they have added another 10 new areas of DNA now known to be associated with risk of type 2 diabetes. They say that their findings support the idea that much of the variation in people’s susceptibility to type 2 diabetes may be due to a large number of common genetic variations, with most of the variations having only a modest effect.

 

Conclusion

This large study has found further genetic variations that may contribute to susceptibility to type 2 diabetes. These findings support current understanding about the complexity of the genetic contribution to this disease – with many different variations contributing only a relatively small effect.

The variations identified by the researchers as being associated with the disease do not necessarily themselves affect type 2 diabetes risk. They may instead lie close to other variations that have the effect. The researchers have identified a number of genes near to these variations that may be responsible, and will need to carry out further research to confirm this.

It is hoped that having a greater understanding of how type 2 diabetes develops may help researchers to develop new treatments. However, it is clear that genetics of type 2 diabetes is complex and the results of the current study do not automatically guarantee new treatments. Much more research will be needed to see if these results can be translated into successful treatments.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on twitter.

Morris AP, Voight BF, Teslovich T, et al. Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. Nature Genetic. Published online August 12, 2012

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