A genetic risk factor for type 2 diabetes commonly found in the DNA of Mexican and Latin American people was likely inherited from Neanderthals when they interbred with humans some 50,000 years ago, according to an exhaustive new analysis.
Scientists at the Broad Institute, a Cambridge genomic research center, worked with colleagues to compare more than 9 million spots in the genomes of 8,000 Latin Americans and found a version of a gene that increased a person’s risk for the disease by about 20 percent. The research, published Wednesday in the journal Nature, was supported by Mexican billionaire Carlos Slim Helú, who visited the Broad Institute this fall to announce a $74 million gift for continued genetics research in Latin American populations.
At the time, Eric Lander, director of the Broad Institute, pointed to this result—which was not yet published—as an example of the importance of studying the genomes of diverse populations, because genetic risk factors for diseases may not be the same.
“It had been missed in all the studies of European patients, and yet it turns out to be one of the most powerful genes that is known to affect diabetes,” Lander said then. “The abstract idea that studying Mexican populations would lead to discoveries that are being missed turns out to be right.”
Mexican and Latin American people have about twice the rate of diabetes as non-Hispanic white people in the U.S., leading researchers to wonder whether there were different genetic risk factors. By comparing the same 9.2 million spots in the DNA of Mexican and Latin American people with and without diabetes, they were able to identify a number of versions of genes more common in people with the disease. Many of those had already been identified in previous genetic studies of the disease, which have typically been done in European populations. But they were especially intrigued by one new gene strongly associated with the disease, with changes to five letters in a gene called SLC16A11.
That version of the gene was nearly absent from African populations and rarely seen in Europeans. It was found in about 10 percent of Asians, and in about half of Native Americans, raising the suggestion that it entered the human gene pool after humans left Africa.
“We were intrigued, and it eventually dawned on us that archaic interaction”—crossbreeding with Neanderthals—“might be the source of this,” said Amy Williams, a post-doctoral researcher at the Broad and Harvard Medical School. Williams and colleagues got access to a new Neanderthal genome sequence and found it there, suggesting that the version of the gene entered the human population when the two species interbred.
That doesn’t suggest that Latin Americans have any more or less Neanderthal DNA than the rest of us. Studies have found that people outside Africa have roughly the same small amount—2 percent of Neanderthal. Williams said analyses suggest that the gene was not adaptive or subject to natural selection, but rose in frequency due to chance—random genetic drift.
The task ahead for the team now is to better understand the role the gene may play in causing the disease. Initial studies revealed that it is active in fat metabolism in the liver, and researchers at the Broad hope to understand the biology to help inform the hunt for therapies.