Identifying Genetic Determinants of Diabetes in African Americans.
The global burden of type 2 diabetes is borne disproportionately by people of non-European ancestry, especially African Americans. But those racial and ethnic disparities have received little attention from genetics researchers.
Now, a new multi-ethnic study by an international team, led by researchers from the School of Public Health and Massachusetts General Hospital, has found that African Americans and whites share some genetic determinants of Type 2 diabetes, while also carrying some unique genetic loci.
The study, published online in the American Journal of Human Genetics, found that about half of gene variants identified in people of European ancestry were shared by African Americans, suggesting that “genetic determinants of human glucose regulation are more similar than different across human populations.”
The study also identified two new genetic variants, bringing to 56 the number of Type 2 diabetes fasting-glucose and fasting-insulin-associated loci.
Ching-Ti Liu, a lead author and associate professor of biostatistics, said the study is an important step to illuminating genetic variation underlying type 2 diabetes, which affects more than 400 million people globally.
“Racial and ethnic differences in diabetes have been understudied,” Liu said. “We feel strongly that the trans-ethnic approach, combined with the genomic annotation information we used, will lead the way forward to understand the implications of the genetic variations underlying type 2 diabetes and other complex disorders.”
Co-author James Meigs of Massachusetts General Hospital and Harvard Medical School said the research team assembled the largest-ever collection of genetic information and fasting glucose and insulin levels on non-diabetic African American individuals.
“We combined this with a massive collection of white individuals that we had previously assembled, and with this resource, were able to define, to a very advanced degree, the common genetic underpinnings of glucose and insulin regulation,” he said. “This project sought to redress the health disparity conferred by the understudy of African Americans—and in addressing the disparity, we have revealed, in a new way, the genetics of glucose regulation that are shared, as well as unique, across humans.”
The number of people with diabetes worldwide has risen from 108 million in 1980 to more than 400 million. In the same period, the global prevalence of diabetes among adults over 18 years of age has risen from 4.7 percent to 8.5 percent. Diabetes prevalence has been rising more rapidly in middle- and low-income countries.
Type 2 diabetes is the most common form of the disease. Diabetes is a major cause of blindness, kidney failure, heart attacks, stroke, and lower limb amputation.
The new study analyzed data from more than 30,000 individuals of African ancestry and combined those findings with results from more than 57,000 people of European ancestry (EA). Fasting blood samples were obtained from all participants, and genetic associations were analyzed.
The research team analyzed the variations in DNA nucleotides, known as SNPs, and narrowed the genomic interval containing the likely causal variants underlying fasting glucose and insulin levels. The study found that many of the genetic variants associated with fasting glucose and insulin levels are likely to have a regulatory function, with few having a predictive protein-coding function.
Knowing the regulatory function may help to identify regulatory pathways that are amenable to manipulation, opening possibilities for type 2 diabetes prevention and control, Liu said.
In the US, more than 29 million people have diabetes, up from the previous estimate of 26 million in 2010, according to the Centers for Disease Control and Prevention. Another 86 million adults—more than one in three US adults—have pre-diabetes. One in four people with diabetes doesn’t know he or she has it.
The study was conducted by the African American Glucose and Insulin Genetic Epidemiology Consortium, co-led by Liu and Meigs. The group has researchers from dozens of institutions in the US and internationally.
Co-authors from SPH include: Jaeyoung Hong, formerly a research assistant and doctoral student in biostatistics; Denis Rybin, statistical coordinator at the Data Coordinating Center; and Josée Dupuis, professor of biostatistics.
Comments & Discussion
Boston University moderates comments to facilitate an informed, substantive, civil conversation. Abusive, profane, self-promotional, misleading, incoherent or off-topic comments will be rejected. Moderators are staffed during regular business hours (EST) and can only accept comments written in English. Statistics or facts must include a citation or a link to the citation.