Right Intervention for the Right Population

Diseases with a unique genetic basis in Asian populations reveal opportunities for precision public health approaches in the region.

Our genetic makeup, environmental conditions and lifestyle habits are responsible for the myriad of differences that make us individuals. These differences include even our susceptibility to disease: some illnesses, for example, are more likely to affect certain ethnic groups over others.

With precision medicine’s multifaceted data-driven approach, doctors now have a better understanding of how disease risk differs in patient populations. Public health, which aims to improve community health at the population level, stands to benefit greatly from such an approach. “Healthcare will always be characterised by infinite demand and very finite resources,” said Dr Jeremy Lim in the introduction to the Precision Public Health Asia 2021 Virtual Conference. Lim is the Founding President of the Precision Public Health Asia Society and Director at the Leadership Institute for Global Health Transformation at the National University of Singapore Saw Swee Hock School of Public Health.

“Precision public health… will allow us to know who needs what, at what point in time, and hence stretch the very limited healthcare dollars,” Lim added. Precision medicine programmes and population-wide genomic studies can inform public health strategies by identifying the genetic factors that make some populations more susceptible than others to a particular disease. In this feature, we look at some notable diseases with a known genetic basis in Asian populations.

 X-linked dystonia-parkinsonism

One intriguing example of a population-specific genetic disease is X-linked dystonia-parkinsonism (XDP), an extremely rare and debilitating movement disorder characterised by tremors, disturbed balance and involuntary muscle spasms. There is currently no cure for XDP and existing treatments offer only temporary relief.

The disease appears to be indigenous to the Philippine island of Panay, with all XDP patients identified so far sharing Filipino roots. While this suggests the disorder can be traced back to a single genetic ancestor, the exact genetic pathways underlying XDP are still unknown. A better genetic understanding of XDP could potentially improve disease control. For example, a 2015 study1 of 166 XDP patients suggests that the disease could be explained by a pathogenic haplotype, a set of gene alterations that are passed down together from parent to child. A precision public health approach could target genetic counselling to people who carry this haplotype.

 Thalassaemia

Southeast Asia, one of the world’s most ethnically diverse regions, is also home to more than 60 different thalassaemia syndromes2. Thalassaemia is a heritable disease caused by gene mutations that lower the body’s production of haemoglobin, a protein crucial for the oxygen-carrying function of red blood cells. Patients with the disorder often feel tired and weak, and in severe cases, can suffer from deformed bones, increased infection risk and heart problems. Patients may also require blood transfusions throughout their life.

The only cure for thalassaemia is a risky bone marrow transplant. Unfortunately, prevention is also difficult due to its complex genetic landscape. This is especially true in Southeast Asia, given the sheer diversity of genetic alterations that give rise to the many variants of the disease. By focusing on the most common mutations in individual countries and communities, rather than a whole-of-region approach, precision public health strategies could one day lead to stronger thalassaemia prevention and control in Southeast Asia.

Diabetes

Even across geographic borders, precision public health can lead to more effective interventions. Take the East Asian population, a highly diverse group that encompasses individuals of Japanese, Chinese and Korean descent. A recent study3 has found that East Asians harbour genetic markers that make them more susceptible to type 2 diabetes than Caucasians. Type 2 diabetes is widely considered a lifestyle disease caused by insulin resistance, lack of exercise and unhealthy diets. As it turns out, some genetic mutations specific to East Asians can impair the way the body uses fat, increasing the risk of type 2 diabetes—even in individuals with a low body mass index.

Leveraging this genomic knowledge, a public health strategy to prevent diabetes in East Asian populations could recommend more stringent lifestyle guidelines, such as more physical activity or diets lower in fat. Routine screening could also be started earlier in this population to identify risk and prevent diabetes before it progresses further.

Rare genetic diseases

A precision public health’s strategy is to decrease disease burden by accounting for diversity. Such a strategy holds promise in South Asia, home to more than 1.5 billion people. In 2017, a large genome-wide study4 of over 2,800 individuals across 260 South Asian groups found over 80 distinct groups of people that each suffer from exceptionally high rates of specific genetic disorders.

For instance, people with Vysya ancestry are around a hundred times more likely to carry mutations that inactivate the butyrylcholinesterase enzyme, making muscle relaxant drugs fatally toxic. Conditions such as butyrylcholinesterase deficiency are so rare that they receive little public and policy attention. A precision public health strategy to address this could take a targeted population-centric approach. The study suggests that doctors could ask their patients if they belong to any ethnic group with known genetic disorders, while public health practitioners could actively survey ancestral communities for familial diseases for early intervention.

Precision medicine, which aims to deliver of the right intervention at the right time to the right population, can help populations across the world: from XDP patients in Panay to diabetics in East Asia and beyond.

References:

1 Domingo, A., Westenberger A., Lee, L.V., Brænne, I., Liu, T., et al. New insights into the genetics of X-linked dystonia-parkinsonism (XDP, DYT3). Eur J Hum Genet 23, 1334-1340 (2015).

2 Fucharoen, S., Winichagoon, P. Haemoglobinopathies in southeast Asia. Indian J Med Res 134(4), 498-506 (2011).

3 Spracklen, N., Horikoshi, M., Kim, Y.J., Lin, K., Bragg, F., et al. Identification of type 2 diabetes loci in 433,540 East Asian individuals. Nature 582(7811), 240-245 (2020).

4 Nakatsuka, N., Moorjani, P., Rai, N., Sarkar, B., Tandon, A., et al. The promise of discovering population-specific disease-associated genes in South Asia. Nat Genet 49, 1403-1407 (2017).