Variant Bio-Led Study Powers Discovery of Extreme Polynesian Founder Effects and Protective Variants in Twin Science and Nature Communications Papers

Variant Bio-Led Study Powers Discovery of Extreme Polynesian Founder Effects and Protective Variants in Twin Science and Nature Communications Papers

PR Newswire

SEATTLE, Oct. 26, 2026

• Research with Stanford and UC San Diego draws on genomic and clinical data from more than 1,000 French Polynesian people
• Polynesian people carry founder effects ten times stronger than in Finland, concentrating both disease-causing and protective gene variants
• Findings include health risks and drug-target leads the world's largest genetic databases miss

SEATTLE, Oct. 26, 2026 /PRNewswire/ -- Variant Bio was founded on the idea that populations with distinctive genetic histories hold discoveries other datasets cannot reveal. Two studies published this month bear that out. In Science, researchers using data from a Variant Bio-sponsored study show that Polynesians experienced founder effects at least ten times stronger than those in Finland, one of genetics' textbook founder populations. In Nature Communications, Variant Bio and partners show what those founder effects make possible: gene-disrupting variants that are nearly absent worldwide but common enough in Polynesia to reveal their effects on human health, including a promising drug-target lead.

Both papers draw on whole genomes from more than 1,000 participants in French Polynesia's Maʻi ʻuʻu study, sponsored by Variant Bio in partnership with clinicians, community leaders, and academic partners across the Pacific.

Science: founder effects ten times stronger than Finland's, and disease variants screening panels miss

The first publication, "Message in a bottleneck," which was featured on the cover of Science, was led by researchers at Stanford University and UC San Diego, with Variant Bio as a co-author. It drew on French Polynesian genomic data from the Maʻi ʻuʻu study, newly sequenced genomes from Rapa Nui, and Native Hawaiian data from the NIH All of Us program. As Polynesians settled island after island, each voyage carried only a small founding group. The result was repeated genetic bottlenecks: Polynesian founder effects proved at least ten times stronger than in Finland, and more intense than in other well-studied founder populations such as the Amish and Ashkenazi Jews. The genomes also show that Hawaiʻi and Rapa Nui, 7,000 km apart, were likely settled by the same voyagers out of Mangareva.

These bottlenecks pushed globally rare variants to high frequency, raising the risk of recessive disease, which has implications for clinical genetics. The study examined three such variants, which cause kidney failure (FAN1), early lens dislocation (ADAMTSL4), and progressive vision loss (PDE6B). Each is carried by 2.2% to 3.7% of French Polynesians. That is four to seven times the threshold at which the American College of Medical Genetics and Genomics recommends population carrier screening. The FAN1 variant does not appear once among the more than 800,000 genomes and exomes in gnomAD. Because the study sampled French Polynesians to represent the general population, these frequencies reflect real disease risk across the islands, high enough to qualify affected Polynesian communities for carrier testing under existing guidelines.

Nature Communications: from founder effect to drug-target lead

The same dynamics that can concentrate disease-risk variants also concentrate protective ones, and that is what makes them relevant for drug discovery. The Nature Communications study, co-led by Variant Bio, paired genomes from over 1,000 participants with deep phenotyping, blood metabolite, and gene-activity profiles. It found hundreds of functional variants with phenotypic and molecular impacts that are absent or rare in global databases.

One standout is a putative loss-of-function variant in ANGPTL8, a regulator of fat metabolism. The variant is found at over 5% frequency in the cohort and is entirely absent in European ancestry groups. Carriers had healthier lipid profiles, lower inflammatory markers, and lower gout risk. Because the variant is so common, the study could observe multiple people with two copies of the variant, a natural model of what drugging the gene might do. By comparison, there are no individuals carrying two copies of a putative ANGPTL8 loss-of-function allele in the UK Biobank, despite its much larger size.

The study also linked a variant near LRMDA to more than double the odds of type 2 diabetes, and implicated WDR1 as a new gene contributing to gout, a disease affecting 14.5% of French Polynesians.

"We started Variant Bio because the biggest datasets miss what underrepresented populations can reveal. These studies show why. Polynesia's founder effects made a protective ANGPTL8 variant common for the first time in any population, so we could observe people with two disrupted copies. Biobanks hundreds of times larger don't include a single one." said Stephane Castel, PhD, Founder and CSO of Variant Bio.

"Gout and diabetes weigh heavily on families in Tahiti, and throughout the world. These findings give us new biology to work with, and they came directly from the people of French Polynesia," said Prof. Tristan Pascart, Hôpital Saint-Philibert, Lille, one of the world's leading rheumatologists and a principal investigator of the Maʻi ʻuʻu study.

Built with communities, shared with communities

The work began in 2021 with a community consultation led by Tahitian consultants across all five French Polynesian archipelagos. That consultation shaped how samples are handled and how findings return to communities. Variant Bio shares research benefits directly with participating communities through financial and community support. The Science authors describe it as the only biotechnology company to date to do so. A committee that includes a Polynesian community representative oversees access to the data.

Co-corresponding Science author Keolu Fox, PhD (UC San Diego) co-authored both papers and is the first Native Hawaiian to earn a PhD in Genome Sciences. "A variant carried by one in 45 French Polynesians was invisible to databases built from more than 800,000 people. That is what underrepresentation costs, and why including Pacific communities changes what medicine can see," he said.

The published analyses cover only part of the data Variant Bio has generated in French Polynesia, and further findings are in progress. Variant Bio is expanding its research partnerships across the South Pacific, and to other regions of the world whose populations share similar genetic histories.

About Variant Bio 

Variant Bio is developing life-saving therapies by studying the genes of people with exceptional health-related traits. By identifying communities with unique genetic architectures and outlier phenotypes, Variant Bio has identified novel human genetic evidence that is the basis for programs with breakthrough potential across multiple therapeutic areas. The company's research is powered by its proprietary Inference platform, which integrates across deep phenotyping and multi-omic data using AI/ML and statistical genetics approaches to identify and validate therapeutic targets. With ethics at its core, the company launched an unprecedented benefit-sharing program in 2020, in which it has pledged tangible benefits that directly impact the communities it partners with throughout the world. Follow Variant Bio's news and updates at www.variantbio.com and via its blog, on X/Twitter @VariantBio, on Instagram @variant_bio, and on LinkedIn.

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