Largest-Ever Gene Study of Type 2 Diabetes Finds Variants across Many Ethnic Groups
he largest genetics study to date of type 2 diabetes (T2D) has identified new gene variants associated with risk for the common metabolic disease. An international scientific consortium, studying multiethnic populations, uncovered genes that may point to biological targets for developing more effective drugs for T2D.
Multiple genes and environmental factors interact with T2D, which affects nearly 300 million people worldwide. The majority of the gene variants remain undiscovered.
“Scientists have identified only about 10 percent of the genetic variants contributing to T2D, and most previous studies have been based on people of European ancestry,” said senior co-author Brendan J. Keating, Ph.D., of the Center for Applied Genomics at The Children’s Hospital of Philadelphia. This international study found that many gene variants associated with T2D overlap across multiple ethnic groups.” The current study included subjects with African-American, Hispanic, Asian and European ancestry.
The study appears online today in the American Journal of Human Genetics. The study’s other senior co-author was Richa Saxena, Ph.D., from Massachusetts General Hospital and Harvard Medical School.
The research consortium performed a meta-analysis of 39 existing studies of multiethnic populations, comprising over 17,000 cases of individuals with T2D, compared to 70,000 control subjects. This large-scale genetic screening used a customized gene analysis tool to examine 50,000 genetic variants across 2,100 genes known to be associated with cardiovascular and metabolic functions.
Diabetes and Ethnicity
Global studies on ethnic groups and minorities and the rising incidence of diabetes have revealed one factor in particular; ethnicity can increase or decrease one’s risk of developing diabetes.
Whilst in some cases this can be explained by access to healthcare and other socio-economic factors, studies have proved that even with equal access prevalence of diabetes differs between people of different ethnicity.
Ethnicity facts
Type 2 diabetes is up to 6 times more likely in people of South Asian descent
Type 2 diabetes is up to three times more likely in African and Africa-Caribbean people
Furthermore, diabetes affects different ethnic groups in different ways.
The researchers identified variants in four previously unknown genes associated with T2D, discovered six new independent genetic signals in known T2D genes, and verified 16 previously reported T2D-linked variants. A total of nearly 40 gene variants have now been found to raise or lower the risk of T2D. Keating says the current study’s genome-wide screening approach in large multi-ethnic samples should be effective in discovering additional diabetes gene variants relevant to multiple ethnic populations.
Type 2 diabetes, previously called non-insulin dependent diabetes or adult-onset diabetes, accounts for 90 to 95 percent of all diabetes. It is a chronic metabolic disease in which the body produces insufficient insulin or becomes unable to properly process insulin it does produce. While the risk of T2D generally rises with age, the disorder has been significantly increasing among children and adolescents.
Diabetes and ethnic minorities
The global prevalence of diabetes for all age groups is estimated to be 2.8%. Type 2 diabetes accounts for at least 90% of diabetes worldwide. Diabetes incidence, prevalence, and disease progression varies by ethnic group.
Diabetes mellitus is a heterogeneous disease, characterised by metabolic disorders manifesting as relative or absolute deficiency of insulin. These conditions lead to cardiovascular, cerebral, and renal vascular disease, primarily through other risk factors, mainly high blood pressure, dyslipidaemia, and inflammation. While ethnicity has clear effects on the prevalence and incidence, aggressive management of these risk factors produces important benefits in all ethnic groups.
The origin of the ethnic differences in incidence remains unclear but does not seem to be clearly genetic: intergenerational social factors seem to modulate the biology of the disease and its evolution and these should be amenable to treatment and prevention in all ethnic groups worldwide.
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J Oldroyd, M Banerjee, A Heald, K Cruickshank
“As we continue to identify more genes associated with type 2 diabetes, we expect that further investigation of their specific biological functions will guide researchers toward new therapies for preventing and treating this disease,” said Keating.
The two main groups funding this study were the National Heart, Lung and Blood Institute of the National Institutes of Health through the Candidate Gene Association Resource (CARe) study and the British Heart Foundation. Many other funding sources supported the 39 studies contributing data to this meta-analysis. Among other senior investigators from The Children’s Hospital of Philadelphia were Hakon Hakonarson, M.D., Ph.D., director of the Center for Applied Genomics, and Struan F.A. Grant, Ph.D., associate director of that center.
“Large-Scale Gene-Centric Meta-Analysis across 39 Studies Identifies Type 2 Diabetes Loci,” American Journal of Human Genetics, published online Feb. 9, 2012, to appear in print, March 9, 2012. doi: 10.1016/j.ajhg.2011.12.022
About The Children’s Hospital of Philadelphia: The Children’s Hospital of Philadelphia was founded in 1855 as the nation’s first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals and pioneering major research initiatives, Children’s Hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country, ranking third in National Institutes of Health funding. In addition, its unique family-centered care and public service programs have brought the 516-bed hospital recognition as a leading advocate for children and adolescents.
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Source: Children’s Hospital of Philadelphia