Shape of cerebral cortex can predict genetic ancestry

The three-dimensional shape of the cerebral cortex can strongly predict an individual’s genetic ancestry, even after generations of migratory and “melting pot” influences, according to researchers at the University of California San Diego School of Medicine, in San Diego.

“The geometry of the brain’s cortical surface contains rich information about ancestry,” said the study’s first author, Chun Chieh Fan, MD, a graduate student in cognitive science. “Even in the modern contemporary U.S. population, with its melting pot of different cultures, it was still possible to correlate brain cortex structure to ancestral background.”

What’s so important about mapping an individual brain to determine its genetic ancestry? It could provide a kind of benchmark against which that brain’s particular differences would be revealed.

“If we can account for a large percentage of brain structure based on an individual’s genes, we’re in a better position to detect smaller variations in the brain that might be important in understanding disease or developmental issues,” said the study’s senior author Anders Dale, PhD, professor of radiology, neurosciences, psychiatry and cognitive science, and director of the Center for Translational Imaging and Precision Medicine at UC San Diego.

The study, published online in Current Biology, opens the door to more precise studies of brain anatomy going forward and could eventually lead to more personalized medicine approaches for diagnosing and treating brain diseases. 

To carry out the study, the researchers analyzed the data of 562 children aged 12 years and older (a group chosen because the cortex surface changes little after age 12) culled from the Pediatric Imaging, Neurocognition and Genetics (PING) study.

Four continental populations were used as ancestral references: European, West African, East Asian and Native American.

The researchers took the children’s neuroimaging scans and used brain imaging analysis software to map the shape of the cerebral cortex. When the results were compared to the individuals’ genetic data, patterns linked to genetic lineage emerged. 

“We looked to see how well we could predict how much genetic ancestry they had from Africa, Europe, and so forth,” said study co-author Terry Jernigan, PhD, professor of cognitive science, psychiatry and radiology, adding that cortex differences between various lineages were focused in certain areas. “There were various systematic differences, particularly in the folding and gyrification patterns of the cortex. Those patterns were quite strongly reflective of genetic ancestry.” 

The metrics for summarizing genetic ancestry in each ancestral component were standardized as proportions ranging from 0% to 100%. The researchers reported that the cortical patterns accounted for 47% to 66% of the variation among individuals in their genetic ancestry, depending on the ancestral lineage.

“There was a lot of variability in our participant population,” Dr. Jernigan said, explaining that the children’s genetic results ran along a continuum, where a child might be 40% one lineage and 60% another. 

Dr. Dale said the differences in cortex shapes between the various ancestries are “subtle, but systematic.” He said understanding these differences will be important in refining future brain research and also in creating appropriate standards of comparison for the various ancestral groups, and for those which are a mixture of different groups.

Dr. Jernigan said, “In order to understand what might be abnormal for a particular individual, it is very important to control for the differences in brain structure that are simply reflective of genetic ancestry. We need to develop better genetically informed analysis for detecting abnormalities in the brain and for measuring differences in the brain that might account for disease symptoms. This study is a step in the right direction and has implications for how people conduct brain research going forward.”