Nav: Home

Type 2 diabetes genetic mapping identifies new 'loci'

May 04, 2017

Scientists are closer to understanding the genetic causes of type 2 diabetes by identifying 111 new chromosome locations ('loci') on the human genome that indicate susceptibility to the disease, according to a UCL-led study in collaboration with Imperial College London.

Type 2 diabetes is the world's most widespread and devastating metabolic disorder and previously only 76 loci were known and studied. Very few these loci are found in the African American population where the prevalence of type 2 diabetes is almost twice that in the European American population (19% vs. 10%).

Of the additional 111 loci identified by the team, 93 (84%) are found in both African American and European populations and only 18 are European-specific.

The study, published today in the American Journal of Human Genetics, used a method developed at UCL based on highly informative genetic maps to investigate complex disorders such as type 2 diabetes.

European and African American sample populations comprising 5,800 type 2 diabetes case subjects and 9,691 control subjects were analysed, revealing multiple type 2 diabetes loci at regulatory hotspots across the genome.

"No disease with a genetic predisposition has been more intensely investigated than type 2 diabetes. We've proven the benefits of gene mapping to identify hundreds of locations where causal mutations might be across many populations, including African Americans. This provides a larger number of characterised loci for scientists to study and will allow us to build a more detailed picture of the genetic architecture of type 2 diabetes," explained lead author, Dr Nikolas Maniatis (UCL Genetics, Evolution & Environment).

"Before we can conduct the functional studies required in order to better understand the molecular basis of this disease, we first need to identify as many plausible candidate loci as possible. Genetic maps are key to this task, by integrating the cross-platform genomic data in a biologically meaningful way," added co-lead author, Dr Toby Andrew (ICL, Department of Genomics of Common Disease).

The team discovered that the additional 111 loci and previously known 76 loci regulate the expression of at least 266 genes that neighbour the identified disease loci. The vast majority of these loci were found outside of gene coding regions but coincided with regulatory 'hotspots' that alter the expression of these genes in body fat.

They are 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.

Three loci present in African American and European populations were analysed further using deep sequencing in an independent sample of 94 European patients with type 2 diabetes and 94 control subjects in order to identify genetic mutations that cause the disease.

The team found that all three loci overlapped with areas of the chromosome containing multiple regulatory elements and epigenetic markers along with candidate causal mutations for type 2 diabetes that can be further investigated.

"Our results mean that we can now target the remaining loci on the genetic maps with deep sequencing to try and find the causal mutations within them. 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 just confined to Europeans," added Dr Winston Lau (UCL Genetics, Evolution & Environment).

"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," concluded Dr Maniatis.
-end-


University College London

Related Diabetes Articles:

Tele-diabetes to manage new-onset diabetes during COVID-19 pandemic
Two new case studies highlight the use of tele-diabetes to manage new-onset type 1 diabetes in an adult and an infant during the COVID-19 pandemic.
Genetic profile may predict type 2 diabetes risk among women with gestational diabetes
Women who go on to develop type 2 diabetes after having gestational, or pregnancy-related, diabetes are more likely to have particular genetic profiles, suggests an analysis by researchers at the National Institutes of Health and other institutions.
Maternal gestational diabetes linked to diabetes in children
Children and youth of mothers who had gestational diabetes during pregnancy are at increased risk of diabetes themselves, according to new research published in CMAJ (Canadian Medical Association Journal).
Two diabetes medications don't slow progression of type 2 diabetes in youth
In youth with impaired glucose tolerance or recent-onset type 2 diabetes, neither initial treatment with long-acting insulin followed by the drug metformin, nor metformin alone preserved the body's ability to make insulin, according to results published online June 25 in Diabetes Care.
People with diabetes visit the dentist less frequently despite link between diabetes, oral health
Adults with diabetes are less likely to visit the dentist than people with prediabetes or without diabetes, finds a new study led by researchers at NYU Rory Meyers College of Nursing and East Carolina University's Brody School of Medicine.
Diabetes, but not diabetes drug, linked to poor pregnancy outcomes
New research indicates that pregnant women with pre-gestational diabetes who take metformin are at a higher risk for adverse pregnancy outcomes -- such as major birth defects and pregnancy loss -- than the general population, but their increased risk is not due to metformin but diabetes.
New oral diabetes drug shows promise in phase 3 trial for patients with type 1 diabetes
A University of Colorado Anschutz Medical Campus study finds sotagliflozin helps control glucose and reduces the need for insulin in patients with type 1 diabetes.
Can continuous glucose monitoring improve diabetes control in patients with type 1 diabetes who inject insulin
Two studies in the Jan. 24/31 issue of JAMA find that use of a sensor implanted under the skin that continuously monitors glucose levels resulted in improved levels in patients with type 1 diabetes who inject insulin multiple times a day, compared to conventional treatment.
Complications of type 2 diabetes affect quality of life, care can lead to diabetes burnout
T2D Lifestyle, a national survey by Health Union of more than 400 individuals experiencing type 2 diabetes (T2D), reveals that patients not only struggle with commonly understood complications, but also numerous lesser known ones that people do not associate with diabetes.
A better way to predict diabetes
An international team of researchers has discovered a simple, accurate new way to predict which women with gestational diabetes will develop type 2 diabetes after delivery.
More Diabetes News and Diabetes Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Clint Smith
The killing of George Floyd by a police officer has sparked massive protests nationwide. This hour, writer and scholar Clint Smith reflects on this moment, through conversation, letters, and poetry.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Dispatch 6: Strange Times
Covid has disrupted the most basic routines of our days and nights. But in the middle of a conversation about how to fight the virus, we find a place impervious to the stalled plans and frenetic demands of the outside world. It's a very different kind of front line, where urgent work means moving slow, and time is marked out in tiny pre-planned steps. Then, on a walk through the woods, we consider how the tempo of our lives affects our minds and discover how the beats of biology shape our bodies. This episode was produced with help from Molly Webster and Tracie Hunte. Support Radiolab today at Radiolab.org/donate.