Population study in the state of São Paulo suggests predisposition to obesity and diabetes

An analysis performed with 264 people living in and around Campinas mapped 900,000 genetic markers distributed in their genomes. It aimed to lay the foundations for precision medicine and provide input for public health policy.

By José Tadeu Arantes  |  Agência FAPESP – The population of Campinas and other cities in the state of São Paulo (Brazil) may have acquired a genetic predisposition to accumulate sugar and fat in their bodies through past evolutionary adaptations and hence to develop diseases such as obesity and diabetes, according to a study published in Scientific Reports by researchers affiliated with the Brazilian Institute of Neuroscience and Neurotechnology (BRAINN) at the University of Campinas (UNICAMP). BRAINN is one of the Research, Innovation and Dissemination Centers (RIDCs) supported by FAPESP.

The principal investigator for the study was Iscia Lopes-Cendes, who heads the Molecular Genetics Laboratory at UNICAMP’s Medical School.

The study was conducted under the auspices of the Brazilian Initiative on Precision Medicine (BIPMed), also supported by FAPESP.

“We mapped some 900,000 genetic markers distributed in the genomes of 264 people from Campinas [the most populous city in the interior of the state of São Paulo]. The study was the first ever conducted with this level of resolution in Brazil. Most ancestry studies of the Brazilian population use no more than 40 markers,” Lopes-Cendes told Agência FAPESP.

The researchers obtained genomic data from volunteers who had no specific disease but represented the genetic diversity of patients attending UNICAMP’s general hospital (Hospital de Clínicas). The sample was designed for use in a detailed exploration of local ancestry, a technical term in which “local” refers not to geographic but to genomic or chromosomal location. Thus, the researchers explored all genomic regions in search of each marker’s origin, in this case European, African or Amerindian.

“Until we did the study, we had no idea of the enormous variability in the distribution of local ancestry in the Brazilian population, which took us by surprise,” Lopes-Cendes said.

Because descendants of immigrants from southern Europe, especially Italy, account for a large proportion of São Paulo State’s population, markers of European origin predominated in the mapped genomes, accounting for some 80% of the total. The remaining 20% were distributed roughly half and half between African and Amerindian ancestry.

But what particularly intrigued the researchers and motivated the Scientific Reports article was that the 10% Amerindian ancestry provided the most significant element from a public health standpoint: the gene PPP1R3B, which is associated with an organism’s ability to store sugar and fat and hence indicates a predisposition to obesity and related metabolic syndromes such as type 2 diabetes.

“We analyzed the distribution of local ancestry and discovered it was fairly homogeneous in most of the genome except a specific region of chromosome 8, where the gene PPP1R3B is located. In this region, we found a higher proportion of segments of Amerindian origin and a significantly lower proportion of segments of European and African origin,” Lopes-Cendes said. “This required a great deal of calculation and double-checking. It was hard work in terms of mathematics, but it led us to the conclusion that there really is a deviation of local ancestry in this region.”

To explain the deviation, the researchers formulated the hypothesis that this region of chromosome 8 had probably been submitted in the past to a process of selective pressure as the people concerned adapted to the environment. At a time of food scarcity, the gene PPP1R3B, which is associated with sugar and fat storage, may have given its bearers an evolutionary advantage, enabling them to live longer, reproduce more, and pass this trait on to their descendants.

However, a past advantage may have become a present problem in the context of high calorie intake and sedentary lifestyles, aggravated by habits such as tobacco smoking and excessive alcohol consumption.

“This information is of the utmost importance from a public health standpoint,” Lopes-Cendes said. “Our hypothesis was that the population of the Campinas region – and we’re confirming this for populations in other regions of the state of São Paulo – has an augmented genetic predisposition to obesity and its complications. If I were a public health system administrator in the region, I would put strong emphasis on obesity and diabetes prevention programs, with specific teams to promote changes in dietary habits, encourage people to get physical exercise, and warn them of the dangers of smoking and alcohol consumption.”

Precision medicine

With this in mind, Lopes-Cendes presented the findings of the study in different forums, dialoguing with academics in the health sector, especially in the field of epidemiology. “It’s a process we call ‘implementation science or medicine’. In other words, we’re seeking to implement in practice, especially in medical practice, the things we’ve discovered in scientific research,” she said.

“Our main goal is to make good use of research findings in precision medicine. Given the highly heterogeneous and genetically mixed makeup of the Brazilian population, any health center that wants to implement precision medicine practices will very probably have to do this kind of study for its own population of interest. Genetic mapping of this kind is very important because we know in medicine that a greater or lesser predisposition to this or that disease depends on the presence of certain genes in specific regions of the genome – in other words, on local ancestry.”

The study was conducted as part of the postdoctoral research of Rodrigo Secolin, the lead author of the article and a FAPESP scholarship holder.

The article “Distribution of local ancestry and evidence of adaptation in admixed populations” by Rodrigo Secolin, Alex Mas-Sandoval, Lara R. Arauna, Fábio R. Torres, Tânia K. de Araujo, Marilza L. Santos, Cristiane S. Rocha, Benilton S. Carvalho, Fernando Cendes, Iscia Lopes-Cendes and David Comas can be read at www.nature.com/articles/s41598-019-50362-2.