In the most comprehensive genetic study of the Mexican population to date, researchers from UC San Francisco and Stanford University, along with Mexico's National Institute of Genomic Medicine (INMEGEN), have identified tremendous genetic diversity, reflecting thousands of years of separation among local populations and shedding light on a range of confounding aspects of Latino health

The study, which documented nearly 1 million genetic variants among more than 1,000 individuals, unveiled genetic differences as extensive as the variations between some Europeans and Asians, indicating populations that have been isolated for hundreds to thousands of years. These differences offer an explanation for the wide variety of health factors among Latinos of Mexican descent, including differing rates of breast cancer and asthma, as well as therapeutic response. "Over thousands of years, there's been a tremendous language and cultural diversity across Mexico, with large empires like the Aztec and Maya, as well as small, isolated populations," said Christopher Gignoux, PhD, who was first author on the study with Andres Moreno-Estrada, first as a graduate student at UCSF and now as a postdoctoral fellow at Stanford. "Not only were we able to measure this diversity across the country, but we identified tremendous genetic diversity, with real disease implications based on where, precisely, your ancestors are from in Mexico." For decades, physicians have based a range of diagnoses on patients' stated or perceived ethnic heritage, including baseline measurements for lung capacity, which are used to assess whether a patients' lungs are damaged by disease or environmental factors. In that context, categories such as Latino or African-American, both of which reflect people of diverse combinations of genetic ancestry, can be dangerously misleading and cause both misdiagnoses and incorrect treatment. While there have been numerous disease/gene studies since the Human Genome Project, they have primarily focused on European and European-American populations, the researchers said. As a result, there is very little knowledge of the genetic basis for health differences among diverse populations. "In lung disease such as asthma or emphysema, we know that it matters what ancestry you have at specific locations on your genes," said Esteban González Burchard, M.D., M.P.H., professor of Bioengineering and Therapeutic Sciences, and of Medicine, in the UCSF schools of Pharmacy and Medicine. Burchard is co-senior author of the paper with Carlos Bustamante, PhD, a professor of genetics at Stanford. "In this study, we realized that for disease classification it also matters what type of Native American ancestry you have. In terms of genetics, it's the difference between a neighborhood and a precise street address." The researchers focused on Mexico as one of the largest sources of pre-Columbian diversity, with a long history of complex civilizations that have had varying contributions to the present-day population. Working collaboratively across the institutions, the team enlisted 40 experts, ranging from bi-lingual anthropologists to statistical geneticists, computational biologists and clinicians, as well as researchers from multiple institutions in Mexico and others in England, France, Puerto Rico and Spain.