Researchers at the Stanford School of Medicine have found that ethnicity and geography may influence human molecular makeup — from metabolism and immunity to gut microbiota and biological aging.
The findings, which will publish in Cell on May 14, illuminate the complex interplay between genetics and the environment, providing insights for researchers and clinicians seeking to better understand health care for diverse populations. The preliminary findings offer new leads for additional exploration into how one's ethnicity and environment affect many aspects of their biology. Michael Snyder , PhD, the Stanford W. Ascherman, MD, FACS Professor in Genetics, is a co-senior author of the study. Nasim Barapour, PhD, a research scientist, is a co-lead author.
The study employed a sweeping analytical approach, measuring a variety of molecules in the human body — including lipids, microbes, proteins and metabolites (molecules that represent one's metabolic activity) — to construct a new view of human molecular diversity across populations and geographies.
"For the first time we have deeply profiled people from around the world," Snyder said. "This enables us to see what properties such as metabolites and microbes are correlated with ethnicity and which ones with geography."
A global molecular portrait
The researchers analyzed samples from 322 healthy individuals — all attending a conference together — of European, East Asian and South Asian ancestry living in Asia, Europe and North America. Having participants of the same ethnic background but different geographic locations allowed the researchers to disentangle the effects of genetic ancestry from those of environment.
The study identified some ethnicity-associated molecular signatures: South Asian participants showed higher levels of pathogen exposure, for example, while individuals of European ancestry displayed greater gut microbial diversity and elevated levels of metabolites associated with cardiovascular disease. These patterns held regardless of where participants lived, pointing to a strong genetic component in shaping human molecular identity.
Where people live also leaves a measurable imprint on biology. Geographic relocation, meaning those who no longer live on the continent of their ancestors, was associated with significant shifts in metabolic and lipid networks — including cholesterol, bile acid and arachidonic acid pathways — as well as selective changes in the gut microbiome.
One of the study's most striking discoveries, Snyder said, concerns the relationship between geography and biological age — a measure of how old the body's cells and tissues appear at the molecular level, which can differ from chronological age.
"East Asians who live outside of Asia have a higher biological age than those residing in Asia. For Europeans, those residing outside of Europe are younger," Snyder noted.
These divergent aging patterns underscore how the environment may modulate biological age, and they raise important questions about lifestyle, diet and microbiome factors that may accelerate or slow the aging process.
Novel molecular connections
Among the study's novel mechanistic findings, researchers identified a link between the expression of a key telomerase gene — associated with cellular aging and longevity — and the gut microbe Oscillospiraceae UCG-002, mediated by sphingomyelin, a lipid molecule. This finding opens avenues for understanding how the gut microbiome may influence aging at the molecular level.
The dataset generated by this study is an open-access resource that will be valuable for advancing precision medicine — tailoring medical treatment to the individual characteristics of each patient, Snyder said. By elucidating how ethnicity and environment interact to shape molecular biology, the findings lay the groundwork for more equitable and effective diagnostics, therapeutics, and preventive strategies for diverse global populations.
Researchers from the Institute for Systems Biology, the University of Alberta, Université du Québec à Montréal, the University of Salamanca, the Medical University of Graz, the KTH Royal Institute of Technology, the University of Manchester, Amrita Vishwa Vidyapeetham (University), Aalborg University and the University of Washington also contributed to this study.
This research was funded by the Anu and BV Jagadeesh Family Foundation, The Embrace Foundation, the Spanish Health Institute Carlos III, CSIC's Global Health Platform, the Danish National Mass Spectrometry Platform for Proteomics and Biomolecular Imaging, the American Diabetes Association, the National Institutes of Health (grants NIGMS R01GM087221, HG007735 and S10OD026936), the National Science Foundation, the Institute for Systems Biology, a Washington Research Foundation Distinguished Investigator Award, the Manchester NIHR Biomedical Research Centre, and the Greater Manchester Comprehensive Local Research Network.
Stanford's Department of Genetics also supported the work.
