[The Guardian] Since the completion of the human genome project in 2003, scientific activities that were unheard-of a decade ago, such as sequencing the genes of a newly emerging virus in days, the ability to screen for inherited diseases and the potential for personalised medicine have all become a part of public health landscape.
Genomics is often associated with the detection of single gene disorders, such as thalassemia and sickle cell anaemia. Momentum is growing for developing countries to harness such technology, but the utility of genomic research is far wider than that: it has the potential to help them tackle the double burden of infectious and non-infectious diseases.
Examples of current research include using genomics to analyse disease outbreaks, examine antibiotic susceptibility and resistance to drugs and identify genetic risk factors for breast cancer. “Genomics is absolutely changing the way we deal with public health issues and as the technology involves gets a lot cheaper, there will be a massive shift in diagnostics towards molecular technology,” said Hilary Burton, director of the Cambridge-based PHG Foundation.
“The problem is that the companies developing pharmaceuticals and diagnostic tests will be more interested in the high-income countries, and it may be hard to get the right focus in terms of the spectrum of conditions people are exposed to. We can expect a lot of developments in obesity and heart disease, for example.”
Diabetes, however, is one disease that is a global attention-grabber, and new genomic insights are particularly relevant to developing countries, home to 80% of the more than 371 million people with diabetes worldwide. China tops the global diabetes league with 90 million people with the disease, followed by India at 61.3 million. If the rate of growth continues at the current pace the global total is expected to top 552 million by 2030.
The T2D-GENES (Type 2 Diabetes Genetic Exploration by Next-generation sequencing in multi-Ethnic Samples) consortium, funded by the US National Institutes of Health comprises 75 scientists from 27 institutions, including researchers in China and India. It is examining issues such as whether the genetic markers that have already been identified as conferring higher risk of diabetes in European populations are also applicable to other ethnic groups; whether there are markets unique to specific populations; and to what extent the same genetic markers confer the same risk when they interact with different environments.
“We know there’s a genetic component to diabetes, there’s often a strong family history of the disease, especially in Asia,” said Dr Ronald Ma, professor in the Department of Medicine and Therapeutics at the Chinese University of Hong Kong. “We know that the heritable component accounts for 70-80% of risk but unfortunately even the 60-odd genetic markers for diabetes that have been discovered over the last seven years still only explain less than 10% of heritability.”
As participants in the T2D-GENES Consortium, Ma and his colleagues are trying to find out what genetic markers are most useful in different populations and he considers both single ethnic and cross-ethic research in this field to be a good investment. However, the impact of low- and middle-income countries of using genomics to identify people most at risk of developing diabetes is not that apparent in the near future, he said.
“We’re researching into the complications of diabetes and here the translation may be more direct, because complications such as blindness, cardiovascular disease and kidney disease are really where the health cost burden comes in.”
The Chinese University of Hong Kong team has a 10,000-strong registry of Chinese type 2 diabetes patients and in this cohort they have identified four genetic markers that are associated with increased risk of developing end-stage renal disease (half of dialysis patients need it because of diabetes-related complications.) Patients with all four mutations have a six-fold higher risk than those with one or none. Stratifying patients into genetic risk groups can be used in decision-making about resource allocation. High-risk patients may be given more frequent check-ups, for example, or held to more stringent blood sugar control limits.
With funding from the Hong Kong government’s innovation and technology fund, the team developed a panel of genetic markers to stratify type 2 diabetes patients according to their risk of kidney complications. The researchers are now looking at whether sharing this information with patients and their doctors leads to better compliance with medication and better blood glucose and risk factors control.
While this research can translate into more cost-effective use of scarce healthcare resources in a developing country grappling with a diabetes epidemic, there are significant barriers for low-income countries to harness genomics.
For low-income countries, the most obvious barrier to adoption is financial: establishing genomics as a part of the health service is expensive, and requires sustainable funding as well as political will. In addition, low-income countries may not have the necessary health care infrastructure and skilled human resources. The regulatory infrastructure, ie, the capacity to regulate drugs and diagnostic tests, laws governing intellectual property rights, the regulation of genetic testing and consumer genomics may also be lacking.
It also raises a raft of new ethical issues. “Genomics allows you to stratify risk and personalise packages of care accordingly. You might do this to provide optimal benefit to individuals whilst minimising risk and you might also do it for cost-effectiveness reasons – to target changes on the people most likely to benefit,” said Burton. “But, where DNA testing is involved this raises questions about what else you might find out (of clinical or other interest, possibly even forensic), and who else might have access to that information.”
For low-income countries there are other issues to take into account. Trust and confidentiality are more difficult to achieve when governance structures are weak, and the potential for the commercialisation of genomics is unlikely to benefit low-income countries in the short term. Although in the long run genomic knowledge can lead to more cost-effective surveillance and screening, the knowledge is expensive to develop and will inevitably have to compete with essential healthcare services for resources.