Reclaiming Asia’s Genomic Destiny

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The completion of the Human Genome Project (HGP) in April 2003 with the publication of the first human genome sequence is probably one of the most significant landmarks in humanity’s quest for knowledge, costing USD three billion across 13 years. But even after nearly two decades, we have barely scratched the surface of the genomic wealth contained within our DNA, but concerted efforts continue to collect, analyse and utilize genomic data.

 

However, one glaring weakness is this field today is the severe lack of diversity in the overall genomic data landscape. Through the HGP itself involved scientists from six countries including Japan and China, the five main sites that sequenced the majority of the human genome were based in the US and the UK.

 

Despite efforts like the Human Genome Diversity Project and the 1000 Genomes Project, today, it is estimated that the vast majority of genomic data collected and deployed in studies globally come from people of European ancestry. Indeed, genomic data from Asian populations – which broadly represents two-thirds of the world population – only comprises 15 percent of all available genomic data globally. Admittedly, this has increased from a woeful 3 percent in 2009 but the gap remains huge.

 

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Given the fundamental importance of genomic data to the advent of precision medicine, this weakness puts Asia on the back foot when it comes to developing and deploying personalized therapies for patients. The problem is even more urgent as a growing body of research has emerged demonstrating that disease prevalence, presentation and prognosis can be markedly different between Caucasian and Asian populations. There are observable and often significant differences in aspects like standard clinical practice, pharmacokinetics, as well as, crucially, the presence of specific disease biomarkers.

 

For instance, researchers have found that across all drugs approved in Japan from 2001 to 2009, the doses approved for use in the West were higher in 32 percent of drugs across all therapeutic classes compared to the doses approved in Japan. This means that not only might precision therapeutics developed globally be less effective in Asian populations, they may also simply be less relevant by virtue of the fact that they do not necessarily address the most pressing healthcare concerns in the region. Even when they do, the need for bridging clinical trials to ensure compatibility and efficacy in Asian populations often lengthens the drug development and approval windows for global therapeutics.

 

Of course, the Asian region itself – comprising 48 countries, by the UN’s count – is impressively heterogenous. In the past couple of years, many Asian governments, having recognized the transformative potential of precision medicine, have launched national and regional programs to remedy this oversight, as well as more generally advance their own capabilities in this groundbreaking field.

 

China, of course, announced its own precision medicine initiative in 2015, a couple of months after the US Precision Medicine Initiative was announced by then-President Barack Obama, pledging a staggering USD 9 billion by 2030. Singapore launched a National Precision Medicine Programme in 2019. More regionally, the GenomeAsia100K initiative is a non-profit consortium launched in 2018, which seeks to sequence the DNA of 100,000 people across Asia. Reference genome datasets have been created by the Koreans, the Japanese and the Chinese, and large biobanks like the BioBank Japan and the China Kadoorie Biobank have also been established.

 

Efforts are also being made to tackle the Asian characteristics of different diseases. For instance, Japan’s National Cancer Center has cooperated with over 200 medical institutions and pharma companies on LC-SCRUM, a nationwide genetic screening project that has screened treatment target genes in over 7,000 lung cancer patients since 2013, contributing to the development of novel therapeutics in Japan. All these are crucial efforts if Asia hopes to reclaim its genetic destiny and truly advance the progress of precision medicine for patients in the region.

 

Ethnic Differences Across Disease

Cancer

Cancer, with its strong genetic component, has understandably benefited most from precision medicine approaches, which makes it even more important for stakeholders to understand and appreciate the variation in cancer prevalence between Asian and Western populations. Notably, gastrointestinal cancers are far more common in Asian populations but very few resources have historically been dedicated to R&D in these areas. Even in globally common cancers like lung cancer, there are differences in terms of the causative underlying mutations. For instance, lung cancer patients from Japan, China and Southeast Asia are known to have a higher incidence of epidermal growth factor receptor (EGFR) mutation. In 2017, the Asia Early Phase Oncology Drug Development Consortium, comprising Japan, China, Taiwan, Singapore and South Korea, was formed to reconcile the disconnect between global cancer R&D priorities and Asian unmet needs.

 

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Diabetes

Shockingly, over 60 percent of the global diabetic population reside in Asia, with nearly half in China and India combined. While the cause is not yet well-understood, studies have established that the average Asian diabetic is leaner compared to his Caucasian counterpart, leading to the epithet “the lean diabetic”. Asian diabetics also tend to be younger – the largest group of diabetics in Asia is people aged between 40 and 59, compared to people aged over 60 in Europe – and more insulin-resistant. As they tend to develop diabetes at younger ages, they also face higher risks of long-term diabetic complications as well as more severe comorbidities over a longer period of time. Some countries like Japan and Taiwan have introduced urine glucose screening programs to diagnose cases of childhood diabetes in an effort to tackle the disease early.

 

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Hepatitis C Virus (HCV)

Infectious diseases, though without a genetic basis, can also benefit from precision medicine approaches. HCV is currently classified into seven different genotypes based on its viral genome sequence, and their prevalence varies significantly across different regions. Genotypes 1 and 3 are common worldwide but in Asia, genotypes 2 and 6 are also fairly common – though there is also significant variation across the different Asian countries. Genotypes 2 and 3 are around three times more likely to respond to combination interferon + ribavirin therapies compared to genotype 1.

 

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