The world's most remote inhabited island has an asthma mystery; scientists traced it to just two settlers who arrived in 1817

The island is so remote from the rest of mankind that the only way to get there is by a six-day ship journey across the South Atlantic. Tristan da Cunha is 1,750 miles from South Africa. There are no airports, no ferry routes, and no new people to mix the gene pool. For scientists trying to crack the genetic code of asthma, this tiny volcanic outcrop has proven to be one of the most extraordinary natural laboratories on the planet.

Zamel and colleagues at the University of Toronto Genetics of Asthma Research Group published a landmark study, ‘Asthma on Tristan da Cunha: looking for the genetic link. The University of Toronto Genetics of Asthma Research Group’s study in the American Journal of Respiratory and Critical Care Medicine found that 57 percent of islanders had partial evidence of asthma and 23 percent had a definitive diagnosis, defined as increased airway responsiveness combined with a positive medical history. In the same study, the researchers examined 282 islanders, or 97% of the total population. This is an unusually broad population coverage for medical research.

The settlers who changed everything
The British garrison left the island in November 1817, though some, including William Glass, stayed behind and formed the basis of a permanent population. In the years that followed, a few shipwreck survivors and other settlers joined them. The current residents are believed to be descended from just 15 outside ancestors who arrived on the island at different times.


What those founders had in their DNA would echo through every generation that came after them. A 2019 study titled ‘Variation at DENND1B and Asthma on the Island of Tristan da Cunha’ in Twin Research and Human Genetics suggested that William Glass and his African wife may have been asthmatic, and may be the source of a genetic founder effect for asthma in that population. The same study found that all individuals have kinship resemblances of at least first-cousin levels due to inbreeding. In other words, once the variant entered the population, it could persist through later generations.

Genealogy mapping showed the islanders are direct descendants of the original settlers, and historical records suggest at least two founders could have been asthmatic, the American Journal of Respiratory and Critical Care Medicine study said.

What the genes are actually saying
This is where the story becomes scientifically interesting and deeply relevant to the estimated 25 million Americans living with asthma today.

For years, scientists have suspected that genetics plays a big role in asthma. But it was complicated to prove in large and diverse populations because of the sheer number of variables: different environments, different diets, different exposures. Most of that is taken away by Tristan da Cunha.

Several independent twin studies of different populations were examined by Meng et al. in a study published in Allergy, Asthma & Immunology Research, and they revealed that the heritability of asthma was in the range of 0.48–0.79, suggesting a considerable contribution of genetics to the development of asthma. The same review also states that genetic factors may explain 40-60% of the variance in allergen-specific immune responses.

The most strongly associated genetic variant was rs2786098, a known regulator of the gene DENND1B, which was found in essentially all 269 current island residents tested in the 2019 study published in Twin Research and Human Genetics. This variant explained about one-third of the trait heritability, with an allelic odds ratio of 2.6. The same study found that 10 out of 12 people with two copies of the high-risk version of this variant were asthmatic.

That is a lot of risk concentration. If a person had two copies of this variant in Tristan da Cunha, it would increase the risk of them developing asthma.

Why this matters beyond one small island
It would be easy to treat Tristan da Cunha as a curiosity, a remote genetic anomaly of no importance to the rest of the world. But that would miss the point entirely.

The Twin Research and Human Genetics study found that the entire island population at the time of examination was one extended family descended from the original founders. That unusual structure is precisely what makes it valuable. In a city of millions, you can't control for environment and relatedness, but on the island, everyone is related, and the environment is relatively uniform, so you can isolate the genetic signal.

Every asthma gene identified through research on Tristan da Cunha is a gene that could be driving asthma in a child in Chicago, a teenager in Houston, or an adult in New York; they just can’t be seen as clearly through the noise of a larger, more diverse population.

Islanders had a word for the condition long before modern medicine arrived: “ashmere.” Records dating to 1923 say it has been the most common complaint on the island. Two centuries on, it still is. But now scientists are finally beginning to understand exactly why, and that knowledge belongs to everyone.