Exploring the evolution of human disease from a metabolic rather than a genetic perspective

A new Yale-led study has found that we can detect not only our ancestors in genes, but also in our metabolism
.

In an analysis of metabolic profiles of healthy American infants, researchers found striking differences between races, which may help screen for genetic metabolic disorders, cystic fibrosis, or decreased thyroid function more accurately
than traditional screening for genetic diseases.

Curt Scharfe, associate professor of genetics at Yale School of Medicine, said, "We don't want to miss a baby who may be sick, and we don't want families to bear the burden and worry
that a false-positive test can bring.
" Curt Scharfe is the senior author
of the study, published in the journal Molecular Genetics and Metabolism.

For the study, Scharfe and colleagues analyzed data from more than 400,000 babies from 17 self-reported racial groups as part of
California's newborn screening program.
Specifically, they wanted to know if these racial differences could be detected in the baby's blood, which are molecules
that provide energy by breaking down body tissues such as food or fat.

This issue has aroused the interest
not only of academia, but also of pediatricians.
For example, babies of African ancestry are known to have higher blood biomarkers than those born to white parents, indicating cystic fibrosis, although babies born to white parents are much
more likely to end up with the disease.
The researchers hope to use ancestry to account for differences in these marker levels, potentially providing a more accurate way to
assess risk than traditional genetic testing.

It is well known that people of African descent have greater genetic diversity than people of other ethnic groups, as they are the descendants of
the world's oldest ancestral population.
Modern humans have migrated from Africa to all parts of the world; Other races are the descendants of these original immigrants, and their DNA is mutated enough to make them genetically identifiable
.

But the researchers found that metabolic lineages can tell a different story
.
For example, while there is a clear line between genetic variants in African Americans and European Americans, the researchers found that the two groups are metabolically closer
.
Conversely, while Japanese and Chinese are genetically closely related, for example, the researchers found greater differences
in their metabolic profiles.

"This demonstrates the role of the environment in our metabolic processes," Scharfe said
.
"Where people have the same culture and food, people have more similar
metabolic profiles.
If people are separated by circumstances such as language or lifestyle, then the differences in metabolism are greater
than the differences in genes.
”

Scharfe warns that more work
needs to be done before the findings can be applied to the clinic.
The researchers analyzed only 41 of the hundreds of metabolites and relied on the parents' own racial genetic reports, which may not always correspond to reality
.

"It's just the first step, but understanding our metabolic ancestors has a promising future," Scharfe said
.

Gang Peng, Andrew J.
Pakstis, Neeru Gandotra, Tina M.
Cowan, Hongyu Zhao, Kenneth K.
Kidd, Curt Scharfe.
Metabolic diversity in human populations and correlation with genetic and ancestral geographic distances.
Molecular Genetics and Metabolism, 2022; 137 (3): 292