By Brittany Wade
November 10, 2022 | Recently, a Yale research team discovered that newborn metabolic screening data could identify human ancestry and help practitioners diagnose genetic diseases.
Scientists have long recognized that individuals with similar ancient geographic backgrounds share genetic characteristics. It is also widely known that certain genetic disorders are more prevalent among specific ethnic groups, often indicating a child’s risk for disease.
Traditional screening measures have been instrumental in detecting genetic disorders. However, the team at Yale discovered that the metabolism—not the genetic code—might help medical professionals make more accurate diagnoses for inherited and congenital diseases.
“We don’t want to miss a baby who is potentially sick, and we don’t want to put families through the burdens and concerns that can stem from a false-positive test,” explains Curt Scharfe, senior author and associate professor of genetics at Yale School of Medicine, as to why new and advanced screening methods are desperately needed.
Metabolites in the bloodstream comprise the plasma metabolome and serve as biomarkers for disease. Just as certain ethnic groups share similarities in genetic sequence, they also demonstrate similarities in blood metabolite concentrations.
Published in Molecular Genetics and Metabolism (DOI: 10.1016/j.ymgme.2022.10.002), the researchers analyzed the metabolic profiles of nearly 400,000 healthy singleton babies from 17 parent-reported ethnic groups: Asian East Indian, Black, Cambodian, Chinese, Filipino, Guamanian, Hawaiian, Hispanic, Japanese, Korean, Laos, Middle Eastern, Native American, Other Southeast Asian, Samoan, Vietnamese, and White. The data were retrieved from newborns enrolled in the California Newborn Screening (NBS) Program, a state-mandated plan that screens for 80 genetic and congenital disorders.
Using machine learning, the team compared the metabolic profiles of each ethnic group to highlight similarities and differences in blood metabolite levels. Overall, 71% of the 41 metabolites examined demonstrated ethnicity-associated differences, confirming that it is possible to determine an infant’s ethnicity based on their metabolic profile alone.
The team also found that some infants maintained high metabolic similarities with babies from ancestral backgrounds significantly different from their own. For example, Black, Native American, and White babies were closely related metabolically but not genetically.
Conversely, Chinese and Japanese American newborns exhibit considerable metabolic differences despite being genetically similar. This phenomenon may be due to the tendency of certain cultures to hold tightly to their country of origin’s customs rather than fully adopting a traditional American lifestyle.
“This attests to the role of environment in forming our metabolism,” said Scharfe. “Where people share the same culture and food, metabolic profiles are more similar. Where people are separated by circumstances, such as language or lifestyles, then differences in metabolism are greater than genetic variations.”
Differences in ethnicity-associated metabolite levels were also determined for each disease biomarker, such as those related to cystic fibrosis, congenital hypothyroidism, and glutaric aciduria type 1—a condition preventing individuals from properly metabolizing specific proteins.
The team found that some ethnic groups expressed the same biomarker to varying degrees, meaning medical professionals should consult the mean biomarker concentrations for each patient’s ethnicity before administering a diagnosis. Furthermore, the average expression levels must be considered for each distinct geographic region and whether the infant’s family adopts the customs of that region.
Medical practitioners can use this new metabolic data to employ precision medicine. For instance, Samoan American infants exhibited higher average concentrations for 33 of the 41 metabolites studied. If a Samoan baby was born with high levels of acylcarnitines—a group of metabolites linked to various heart conditions (Metabolites, DOI: 10.3390/metabo11010051)—a physician may be inclined to issue an incorrect diagnosis if they are unaware that the infant’s “elevated” levels fall within the average range for their ethnicity.
Similarly, Black American babies traditionally contain elevated biomarkers associated with cystic fibrosis, while babies of northern European descent develop the disease at much higher rates. Therefore, screening exams that analyze data against ethnic metabolic norms provide valuable context to prevent false diagnoses.
The team acknowledges that the study had multiple limitations. First, the ethnic groups were parent-reported, but not every individual identifies with the ethnic background primarily indicated by their DNA. Second, some parents—such as those denoted as “Hispanic” on NBS documents—maintain multiple cultural and ancestral identities that do not align with the pre-determined NBS groups.
Third, the team only analyzed 41 metabolites, but scientists estimate that there are over 4,000 compounds comprising the human plasma metabolome (PLoS One, DOI: 10.1371/journal.pone.0016957). “This is just a first snapshot, but understanding our metabolic ancestry has a promising future,” adds Sharfe. Finally, the team hopes to replicate their study using additional biomarkers, each weighted based on their correlation to various ethnic groups and diseases.