Studying Metabolic Disease in Aotearoa: A New Partnership Between Variant Bio and the University of Otago

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Variant Bio

6 min readJan 27, 2021

The University of Otago (Māori: *Te Whare Wānanga o Otāgo*), based in southern New Zealand, is the country’s oldest university. Photo credit: *The New Zealand Herald*

As a Research Professor in the Department of Biochemistry at the University of Otago, New Zealand, I’ve been involved in genetic research for decades now, and am deeply committed to engaging Māori and Pacific communities in the work that I do. In recent years, my research has focused on the genetics of metabolic disease, which includes gout, kidney disease, and diabetes, and is 2–3-fold more prevalent in the Māori and Pacific (Polynesian) populations of Aotearoa New Zealand.¹,²,³ In particular, Māori face a very high frequency of kidney disease, some of which appears unrelated to diabetes,⁴ as well as the highest frequency of gout in the world.⁵ Yet compared with what we know about kidney disease in other populations, we know virtually nothing about the genetic causes in Māori and Pacific populations.

Now, I am joining forces with Drs. Kaja Wasik and Stephane Castel from Variant Bio to study the genetic causes of kidney disease and related metabolic disorders in people of Māori and Pacific ancestry. Our hope is that the information we gain from this study will ultimately lead to both the better use of existing drugs and the development of new drugs and diagnostic tools for kidney disease, thus improving the health of Māori and Pacific communities in particular, as well as people around the world more generally.

Variant’s overarching ethical approach is based on the principles of respect, transparency, consent, collaboration, and benefit. The company practices project co-creation and consultation with partner communities, and is committed to working with local scientists to improve genomic literacy and to maximizing benefits for communities in ways that reflect their own priorities and values. For the purposes of this collaboration with the University of Otago, the Māori and Pacific community will ultimately determine where the benefits are allocated (for example, training Indigenous students in biostatistics).

I first met Kaja and Stephane in February 2019, on a visit to New York City. One month later, in March, they visited my lab at the University of Otago on their way to Tātai Oranga, a conference for Māori and Pacific community members. Kaja and Stephane came here to engage with the Māori community and understand the state of genetic research on metabolic disease in New Zealand. After designing a study proposal together, Kaja, Stephane, and I consulted with the University of Otago Māori Ngāi Tahu Research Consultation Committee and were granted ethical approval from the Health and Disability Ethics Committees under the New Zealand Ministry of Health. We also submitted our project for evaluation to Variant Bio’s external Ethics Advisory Board. We are very serious about appropriate data governance so currently I remain the custodian of the genetic and diagnostic information generated from the recruited cohort and Variant Bio is granted temporary access to the data to collaborate with my group on the analysis. There is a process underway in New Zealand to shift that custodianship from the university and researcher to the community, and I am fully supportive of this process. There are a number of ethical and cultural considerations to take into account, and we make sure that the data is strictly analyzed from a metabolic disease angle and will never be sold by anyone or shared further by Variant Bio. Additionally, any samples that leave New Zealand for processing are promptly returned (together with any sample derivatives) to be disposed of in a culturally appropriate manner in a ceremony where samples are disposed of with inoi (prayer) followed by sharing of kai (food) and kapu tī (“cup of tea”).

Our project is split into two phases. In the first phase, my New Zealand clinical collaborators and I previously recruited thousands of people with and without disease, of Māori and Pacific ancestry, in order to study the genetic causes of kidney disease, gout, and diabetes. The participants shared DNA, serum, and urine samples together with their medical records to contribute to a better understanding of these common diseases, and this was done with a range of Māori and Pacific organizations, workplaces, and communities. We then sequenced the DNA samples with Variant Bio using an innovative combination of high- and low-pass sequencing approaches that allowed us to build a genetic reference panel and very cost-effectively identify novel and known population-specific genetic variants, run genetic associations, and gain insights into potential therapeutic or diagnostic targets for these high-burden diseases.

We are currently completing a scientific publication describing the novel, cost-effective method and hope that it will inspire researchers working with other underrepresented populations in how they run their studies. In a similar vein, we are performing a urine metabolomics analysis that aims to uncover population-specific metabolite profiles relevant to kidney disease progression. If we can identify Polynesian-specific genetic risk factors for kidney disease, we can contribute to improving diagnostics and therapeutics for this continuously underserved and underrepresented population, and move a step closer to implementing precision medicine in New Zealand.

At this point, Variant Bio and I are also starting the second phase of the project, which entails a new recruitment of participants of Māori and Pacific ancestry with kidney disease. The objective of this phase of the study is to perform more whole-genome sequencing, diagnostics, blood, and urine metabolomics, as well as RNA sequencing on the newly collected samples in order to provide a more granular understanding of kidney disease and its progression.

It is very important to me, my New Zealand clinical collaborators, and to Variant Bio’s overarching mission to maximize benefits for the Māori and Pacific communities participating in our study. I have been striving to do so over my engagement with Māori and Pacific communities in New Zealand over the last 15 years. So far, as a result of our partnership, we have been able to sponsor SING 2020, the very first Indigenous Genomics Conference of its kind, which aims to promote Indigenous partnerships in genomic science, and we have a number of ideas for initiatives to sponsor going forward.

SING 2020 conference poster. Credit: The SING Consortium Aotearoa

Variant Bio is a benefit-sharing company and has committed to sharing tangible short-and long-term benefits with the communities involved in this project. In the short term, Variant will contribute a total of $100,000 USD towards initiatives around research, healthcare, education, and environment that benefit Māori and Pacific communities in Aotearoa New Zealand. Once Variant begins to generate revenue (currently it is an early-stage startup), the company has committed to share 4% of its future revenue (meaning income before expenses, as opposed to profit, which refers to income after expenses) every year with all of its partner communities (including Māori and Pacific communities in New Zealand) until the company is acquired or goes public, at which point partner communities will receive 4% of the company’s equity value.

As detailed here by Variant’s CEO Andrew Farnum, “4% is in fact a groundbreaking number, and up until now, no genomics, pharma, or biotech company has ever come close to this amount.” This is also a big part of the reason why I decided to partner with Variant, because of their kaupapa (values and principles). Currently, we are working with Māori and Pacific advisors to determine how best to allocate the remainder of the current and future benefits provided by Variant with Māori and Pacific communities in ways that are meaningful to them. The current discussions are around creating opportunities for Māori and Pacific student training in genetic data analysis and biostatistics. Māui Hudson, a Council member of the Whakatōhea iwi (tribe) and an interdisciplinary researcher based at the University of Waikato in New Zealand, serves on Variant Bio’s Ethics Advisory Board, and has provided important feedback as to how best to ensure Māori engagement and governance within the framework of this project.

This partnership with Variant Bio is mutually beneficial and very complementary. We are a group of geneticists, biostatisticians, medical doctors, and molecular biologists with deep expertise on the studied diseases, implementing new sequencing technologies and innovating on data analysis, and working together with anthropologists and ethicists who ensure that the participating communities benefit from being our partners in this project. I am hopeful that our partnership will lead to better health outcomes for individuals of Māori and Pacific ancestry, and to a greater understanding of metabolic disease more broadly.

Studying Metabolic Disease in Aotearoa: A New Partnership Between Variant Bio and the University of Otago

Written by Tony Merriman