US self-reported race and ethnicity are poor proxies of genetic ancestry

(Press-News.org) Genetic ancestry is much more complicated than how people report their race and ethnicity. New research, using data from the National Institutes of Health’s (NIH) All of Us Research Program, finds that people who identify as being from the same race or ethnic group can have a wide range of genetic differences. The findings are reported June 5 in the Cell Press journal the American Journal of Human Genetics.

As doctors and researchers learn more about how genetic variants influence the incidence and course of human diseases, the study of genetic ancestry has become increasingly important. This research is driving the field of precision medicine, which aims to develop individualized healthcare.

People whose ancestors came from the same part of the world are likely to have inherited the same genetic variants, but self-identified race and ethnicity don’t tell the whole story about a person’s ancestors. NIH’s All of Us Research Program was created in part to address this puzzle and to learn more about how genetic ancestry influences human health.

In the current study, the investigators looked at the DNA of more than 230,000 people who have volunteered to share their health information for All of Us. They compared it to other large DNA projects from around the world using a technique called principal component analysis (PCA) to visualize population structure and help identify genetic similarity between individuals and groups of people. This analysis showed that people in the US have very mixed ancestry, and their DNA doesn’t always match the race or ethnicity they write on forms. Instead of falling into clear groups based on race or ethnicity, people’s genetic backgrounds show gradients of variation across different US regions and states.

This is especially significant for people who identify as being of Hispanic or Latino origin. These people have a wide-ranging blend of ancestries from European, Native American, and African groups. Importantly, genetic ancestry among these people varies across the US in part because of historic migration patterns. For example, Hispanics/Latinos in the Northeast are more likely to have Caribbean (and thus African) ancestry, and those in the Southwest are more likely to have Mexican and Central American (and thus Native American) ancestry.

One specific discovery was that ancestry was significantly associated with body mass index (BMI) and height, even after adjusting for socio-economic differences. For example, West and Central African ancestries were associated with higher BMI, whereas East Africa ancestry was associated with lower BMI. There were similar findings showing that people with ancestral origins from different parts of Europe have different body measurements including height, with northern European ancestry associated with greater height and southern European ancestry associated with shorter height. This suggests that subcontinental differences in ancestry can have opposite effects on biological traits and diseases.

This finding suggests that the subcontinental differences in ancestry between individuals can have opposite effects on biological traits, diseases, and health outcomes, emphasizing the importance of not classifying individuals into broad ancestry groups such as African, European, or Asian. Doing this will help to make this research more accurate and will help to improve the field of precision medicine.

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This work was supported by NIH’s National Human Genome Research Institute, NIH’s National Institute of Diabetes and Digestive and Kidney Diseases, the Office of the Director at NIH, CNPq-Brazil (Conselho Nacional de Desenvolvimento Científico e Tecnológico), and FAPEMIG (Minas Gerais State Research Agency).

American Journal of Human Genetics, Gouveia et al., “Subcontinental genetic variation in the All of Us Research Program: Implications for biomedical research” https://www.cell.com/ajhg/fulltext/S0002-9297(25)00173-9

The American Journal of Human Genetics (@AJHGNews), published by Cell Press for the American Society of Human Genetics, is a monthly journal that provides a record of research and review relating to heredity in humans and to the application of genetic principles in medicine and public policy, as well as in related areas of molecular and cell biology. Visit http://www.cell.com/ajhg. To receive Cell Press media alerts, contact press@cell.com.

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