The Meta-Analyses of Glucose and Insulin Related Traits Consortium (MAGIC) studied the genomes and blood glucose levels of more than 100,000 people of European descent. The findings are published in two papers - one identifying 10 new gene variants and the second three more.
Dr Jim Wilson, (right) an Edinburgh University geneticist team member, told The Times "This is an incredibly important finding. The discovery of these new genes influencing blood-sugar levels is the first step on the important journey to developing new therapies for diabetes."
“Genetic studies like this open the door onto disease mechanisms and pathways we have no other way of discovering, and which are the raw material for intelligent drug design.”
The first study looked for genes influencing metabolism, such as fasting glucose and insulin levels. Researchers analysed 2.5m genetic variants in 21 genome-wide association studies (GWAS). GWAS look for genetic variants linked to diseases and traits. The chances of finding variants subtly associated with a disease increases by studying thousands of genomes.
More than 120,000 people took part in the research to isolate exactly which genes are involved in the control of glucose in the bloodstream. The Scottish contribution, through the research group, ORCADES , is undertaking a two-year study aimed at improving treatment for some of Scotland’s most common life-threatening diseases; heart disease, stroke, diabetes as well as obesity based on over 1,000 adults from Orkney and funded by the Chief Scientist Office of the Scottish Government and the Royal Society.
The study identified five variants linked to Type-2 diabetes. Most affected insulin release by beta cells and not the body's response to insulin levels. This suggests beta cell impairment may have a larger role in Type-2 diabetes than previously believed, according to the authors.
"The hallmarks of Type-2 diabetes are insulin resistance and impaired beta cell," lead author Dr Inês Barroso (left) from UK's Wellcome Trust Sanger Institute, Cambridge said in Science Daily. 'We were intrigued to find that most of the newly found variants influence insulin secretion, rather than insulin resistance. Only one variant, near IGF1, is associated with insulin resistance'.
The second paper found a gene variant that impairs beta cell functioning by analysing 15,000 genomes in nine GWAS. The risk variant in GIPR, a gene that codes for a beta cell-regulating hormone, affected glucose levels two hours after a sugary meal.
The findings highlight the role of 'incretin' hormones, released from endocrine cells in the gut. 'This finding adds to a growing body of evidence implicating the incretin pathways in Type-2 diabetes risk. These pathways, which stimulate insulin secretion in response to digestion of food, may offer a potential avenue for therapeutic intervention', said senior author Dr Richard Watanabe, (right) from the University of Southern California.
Researchers at the University of North Carolina at Chapel Hill liken the development to charting out a genetic map that has led to the discovery of hot spots of the genes involved in type 2 diabetes and other common illnesses, generating a complete map of currently known areas of the genome that control which genes are "turned on" or "off."
"Most of the human genome is uncharted territory - entire stretches of sequence with no clear function or purpose," Dr Jason Lieb, (left) associate professor of biology at UNC, a member of the UNC Lineberger Comprehensive Cancer Centre and a senior author is quoted saying.
Further research is needed to identify other gene variants and to confirm that these variants are also found in non-Europeans. 'Even with the discovery of these variants, we've only explained about 10% of the genetic contribution to fasting glucose in people who do not have diabetes', said Dr Jose Florez (right) from Massachusetts General Hospital and Harvard Medical School, a lead co-author on the first study.
Diabetes affects more than 220m people worldwide. Over 90% of these cases are caused by Type-2 diabetes, where cells fail to recognise and react to insulin, triggering abnormally high levels of glucose in blood. Type-2 is also referred to as late-onset as it typically develops later in life.