Holding the line: why host genomics (and infectious disease) research matters more than ever

One year ago, the PHG Foundation report, Host genomics: lessons for infectious diseases, highlighted the promise of host genomics research for infectious disease. Policy priorities may have changed since then, the evidence has not. The need to advocate for the importance of this research is more important than ever.

What did our report say?

Host genomics – the study of how human genetic variation shapes susceptibility, severity, and outcomes of infection – can help explain why individuals, when exposed to the same pathogen, experience different outcomes.

In Host genomics: lessons for infectious diseases  we synthesised evidence across four pathogens (tuberculosis, HIV, hepatitis C virus, and SARS‑CoV‑2) and found that host genetic insights identify key immune mechanisms that underpin an effective or harmful response to infection. These insights are breadcrumbs of evidence that can enable innovation, particularly clues into the development of vaccines and therapies, or for better risk stratification of high-risk populations.

The success of host genomics research is dependent on having the right infrastructure, consortia and data interoperability in place. The unprecedented large-scale collaboration during the COVID-19 pandemic, taught us what is possible when we enable genomics research. In comparison, research in other infectious diseases has had pockets of success. However, the specificity of findings results in a fragmented, uncoordinated field of research which is divorced from the broader context required for translational success.

Advancing host genomics is difficult due to a combination of biological complexity—driven by host-pathogen co-evolution—and systemic research barriers. While technical and ethical hurdles exist, the primary challenge is structural.

For example, recent large-scale studies relied heavily on biobanks. Because these biobanks are concentrated in high-income countries with established infrastructure, the resulting data is heavily biased toward European populations. Recent efforts to improve population representation are underway, but may not immediately address the data gaps necessary to enable host genomics research. Conversely, smaller studies embedded in clinical care are more targeted but struggle to scale due to a lack of long-term funding. 

To solve this, we need a joined-up approach where sustainable and representative infrastructure is based on broad stakeholder consensus. 

Policy, priority and unravelling progress?

The last year has seen dramatic and far reaching changes to funding of research and public health in the USA. The scale of these decisions is likely to have far reaching consequences for global health and the most immediate impacts are already being seen following the decision to freeze foreign aid disbursements, including key programs tied to the US Agency for International Development (USAID) and its flagship HIV initiative, the President’s Emergency Plan for AIDS Relief (PEPFAR). Efforts to raise funds through other means, such as pledges made in recent months to the Global Fund to Fight AIDS, Tuberculosis and Malaria, go only so far. The burden of disease falls most heavily on the Global South, and the impact and inequities of these choices are stark.

The implications of these changes to funding on host genomics research is not immediately apparent. Host genomics research often is dependent on data collected alongside infectious disease research. Squeezing budgets limits the opportunity of researchers to collect data and prevents further research, such as genotyping which is key to host genomics. This will mostly affect populations already underrepresented in genomic datasets. Rectifying this imbalance is not only a matter of equity but a scientific imperative. Diverse populations reveal genetic and biological insights that are otherwise missing, improving generalisability and translational potential for all. 

Global fundings and implications for health

When writing the Host Genomics report, following the COVID-19 pandemic, governments strongly upheld the role of infectious disease research to guide their decision making. One year on, the global political landscape looks quite different: funding priorities have been shifted and public health budgets have been tightened. The impact of this is already being seen, for example, with incidence of tuberculosis on the rise. In this new context, investing in infectious disease public health is not a luxury, it is a necessity for equitable, effective health strategies. Research, such as host genomics, enables more effective decision making and innovation to refine these efforts for greatest benefit.

Challenging these decisions requires a collective vision of what this research should look like. Representation of research must lead to improved public health innovation for high risk and highly affected populations. This is not a purely benevolent act, because better control of infectious diseases reduces the global burden. In effect, investment globally reduces the local cost of these diseases on our public health system, enabling us to prioritise other critical population health challenges.

Science, equity and strategy

The public health and academic communities have the power to shape policy priorities that enable host genomics research. Now more than ever is the time for host genomics research to be used demonstrate to policy makers the importance of this work. There are examples of success both in terms of insights from host genomics research (particularly emphasising key elements of the immune response) and opportunity for innovation derived from these insights (for example, vaccines that leverage the role of natural killer cells to target HIV). Taking a strategic and coordinated approach – with limited available resources – could provide the use cases that demonstrate the value of host genomics research.

A call to action

We all have a responsibility for driving policy priorities, this includes a vision of the world we would like to see. As we look “one year later,” our recommendations are the same: build a host genomics strategy, standardise and invest in data and infrastructure, fund functional studies and translational research, and centre LMICs in research and deployment.

Enabling host genomics for the global majority requires infectious disease research to be embedded in the communities where the burden is greatest. Deriving benefit from host genomics research necessitates representative populations affected by the respective infectious diseases. This is the core of why we advocate system-wide thinking, recognising that host genomics is one pillar to enable infectious disease research and innovation.