Global Multiomics Study Reveals How Geography and Ethnicity Shape Human Biology

An international team of researchers has completed one of the most comprehensive longitudinal molecular studies of human diversity ever conducted, uncovering how both ethnicity and geography shape human biology at multiple levels — from metabolism and immune function to the gut microbiome and biological aging.

Published in the journal Cell, the study emerged from the Human Personal Omics Profiling (hPOP) project — a global initiative launched through the Human Proteome Organization’s Human Proteome Project (HUPO-HPP). Researchers analyzed molecular data from 322 generally healthy individuals of European, East Asian, and South Asian ancestry living across Asia, Europe, and North America. The work combined a sweeping range of “multiomics” technologies to create a detailed molecular portrait of how genetics and environment interact to influence health and disease risk.

A subset of participants contributed multiple samples over time, allowing researchers to examine how biological profiles changed over time and compare differences across populations and geographies. 

Researchers from the Institute for Systems Biology’s Moritz and Gibbons groups played a key role in the project, contributing expertise in proteomics, systems biology, and microbiome science as part of a global collaboration led by scientists at Stanford School of Medicine and the Human Proteome Organization.

“This study highlights just how dynamic human biology really is,” said Dr. Robert Moritz, ISB professor and co-senior author on the study. “By integrating many different layers of molecular information across diverse populations, we can begin to understand how genetics, environment, diet, and the microbiome interact to shape health in ways we couldn’t previously see.”

A Global Multiomics Portrait

The study employed a broad multiomics approach, simultaneously analyzing genomics, transcriptomics, proteomics, metabolomics, lipidomics, microbiomics, and other molecular data types from participants attending a conference together. That design allowed researchers to separate the effects of ancestry from those of geography and environment.

“Our study is special because for the first time we have deeply profiled people from around the world, including Asia, Europe, and North America,” said Dr. Michael Snyder, professor of genetics at Stanford and co-senior author of the study. “This enables us to see what properties such as metabolites and microbes are associated with ethnicity and which ones with geography.”

The researchers identified clear biological patterns associated with ancestry. South Asian participants, for example, showed higher levels of pathogen exposure, while individuals of European ancestry exhibited greater gut microbial diversity and elevated levels of metabolites linked to cardiovascular disease risk. Importantly, many of these patterns persisted regardless of where participants lived, suggesting a strong genetic component.

At the same time, geography also left a measurable biological imprint.

Participants living outside the regions associated with their ancestral backgrounds showed significant shifts in metabolic and lipid pathways, including cholesterol, bile acid, and arachidonic acid metabolism, as well as selective changes in the gut microbiome.

Unexpected Insights into Biological Aging

Among the study’s most striking findings were differences in biological aging linked to geography.

“One interesting finding is the association of age with geography,” Snyder said. “East Asians that live outside of Asia have a higher biological age than those residing in Asia. For Europeans, those residing outside of Europe are younger.”

Biological age refers to how old the body’s cells and tissues appear at a molecular level, which can differ from chronological age. The findings suggest that environmental factors — including diet, lifestyle, and microbiome composition — may influence aging differently across populations.

The study also uncovered a potential connection between the gut microbiome and cellular aging. Researchers identified an association between the gut microbe Oscillospiraceae UCG-002, a lipid molecule called sphingomyelin, and the expression of a key telomerase-related gene involved in longevity and cellular aging.

“These kinds of systems-level connections are exactly why multiomics approaches are so powerful,” Moritz said. “When you analyze proteins, metabolites, microbes, and other molecular layers together, you can begin to uncover biological relationships that would otherwise remain invisible.”

Advancing Precision Medicine

The researchers say the resulting open-access dataset could become an important resource for the future of precision medicine, helping scientists better understand how molecular differences across populations may influence disease risk, diagnostics, and therapeutic response.

“This study reinforces the importance of ensuring that biomedical research reflects global diversity,” Moritz said. “Understanding the biological variability across populations is essential if we want precision medicine to truly benefit everyone.”

The study brought together researchers from institutions across North America and Europe, including ISB, the University of Alberta, Université du Québec à Montréal, the University of Manchester, KTH Royal Institute of Technology, Aalborg University Hospital, the University of Salamanca, and others.