Imperial College London

Over 100 genetic hotspots linked to type 2 diabetes found, giving disease clues

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Close up photo of diabetes patient using a glucose monitor

Scientists have uncovered 111 new regions of the genes linked to type 2 diabetes, providing clues to the genetic basis of the disease.

Type 2 diabetes is the world’s most common metabolic disorder that leads to early death and poor health outcomes such as nerve damage, blindness and amputation. The risk of developing the disease depends on genetic predisposition as well as lifestyle factors such as an unhealthy diet, physical inactivity, and obesity.

So far, scientists have identified 76 chromosome locations, or ‘loci’, linked to type 2 diabetes, but very few of these regions have previously been implicated in the African American population, where the prevalence of type 2 diabetes is almost twice that of the European American population (19 per cent v 10 per cent). Despite this, most genetic association studies to date have focussed exclusively upon European populations and struggled to replicate risk genes in populations with African ancestry.

Our study goes some way to better understanding type 2 diabetes risks, including in African Americans, and opens up new lines of enquiry that could have implications for potential new treatments and prevention.

– Dr Toby Andrew

School of Public Health

Now, research by Imperial College London and University College London (UCL), has found 111 new regions involved in developing the disease – 93 (84 per cent) of which are found in both African American and European populations. In addition, for risk genes previously only observed in Europeans, the study was able replicate about one third of these genetic locations in African Americans.

The research, published in The American Journal of Human Genetics, compared 5,800 European and African American people with type 2 diabetes against 9,691 control subjects from Europe and the United States.

Dr Toby Andrew, from Imperial’s School of Public Health, and his colleagues from UCL also found that the combined total of regions linked with type 2 diabetes regulate the expression of at least 266 genes in body fat. The researchers are now currently investigating whether these loci alter the expression of the same genes in other tissues such as the pancreas, liver, and skeletal muscle that are also relevant to type 2 diabetes.

Dr Andrew, who is co-lead author of the paper, said: “We know plenty about how lifestyle factors affect the risk of type 2 diabetes, but our picture of the genetic involvement, particularly concerning different ethnic groups, is still incomplete. Our study goes some way to better understanding type 2 diabetes risks, including in African Americans, and opens up new lines of enquiry that could have implications for potential new treatments and prevention.”

Genetic maps: About the study

The study used a method developed at UCL based on highly informative genetic maps to investigate complex disorders such as type 2 diabetes.  Dr Andrew said: “Before we can conduct the further studies required in order to better understand the genetic basis of this disease, we need to identify as many risk genes as possible. Genetic maps are key to this task, as they help to make sense of the cross-platform genetic data in a biologically meaningful way.”

The authors said that they can now more easily target the remaining unidentified genetic locations to more comprehensively try and identify which mutations, genes and molecular pathways might cause type 2 diabetes.

Co-author Dr Winston Lau, of UCL’s Department of Genetics, Evolution & Environment, added: “We are also very excited that most of the identified disease loci appear to confer risk of disease in diverse populations such as African Americans, implying our findings are likely to be universally applicable and not confined to Europeans.”

Dr Nikolas Maniatis, from UCL’s Department of Genetics, Evolution & Environment and co-lead author of the study, concluded: “We are now in a strong position to build upon these genomic results, and we can apply the same methods to other complex diseases such as Alzheimer’s disease.

"High-Resolution Genetic Maps Identify Multiple Type 2 Diabetes Loci at Regulatory Hotspots in African Americans and Europeans", Winston Lau, Toby Andrew and Nikolas Maniatis, published in The American Journal of Human Genetics on 4 May 2017.

See the press release of this article

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Caroline Brogan

Caroline Brogan
Communications and Public Affairs

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Email: caroline.brogan@imperial.ac.uk

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Diabetes, Global-health, North-America, Obesity, Public-health
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