Modeling the 3D geometry of the cortical surface with genetic ancestry

Abstract

Knowing how the human brain is shaped by migration and admixture is a critical step in studying human evolution [1, 2], as well as in preventing the bias of hidden population structure in brain research [3, 4]. Yet, the neuroanatomical differences engendered by population history are still poorly understood. Most of the inference relies on craniometric measurements, because morphology of the brain is presumed to be the neurocranium's main shaping force before bones are fused and ossified [5]. Although studies have shown that the shape variations of cranial bones are consistent with population history [6-8], it is unknown how much human ancestry information is retained by the human cortical surface. In our group's previous study, we found that area measures of cortical surface and total brain volumes of individuals of European descent in the United States correlate significantly with their ancestral geographic locations in Europe [9]. Here, we demonstrate that the three-dimensional geometry of cortical surface is highly predictive of individuals' genetic ancestry in West Africa, Europe, East Asia, and America, even though their genetic background has been shaped by multiple waves of migratory and admixture events. The geometry of the cortical surface contains richer information about ancestry than the areal variability of the cortical surface, independent of total brain volumes. Besides explaining more ancestry variance than other brain imaging measurements, the 3D geometry of the cortical surface further characterizes distinct regional patterns in the folding and gyrification of the human brain associated with each ancestral lineage.

Figure 1. Predicting the proportion of genetic ancestry by cortical surface geometry

YRI: Yoruban, as the West Africa ancestry. CEU: Utah residents with northern and western European ancestry. EA: East Asia. NA: America natives. In all predictive models, the variables have been residualized with respect to the age, age squared, gender, total brain volumes, and scanner used. All models excluded individuals with a 0% proportion of genetic ancestry to that specific component. LOOCV: leave-one-out cross-validation. The colors of the data points are determined by the proportion of genetic ancestry as illustrated in the figure legend.

Figure 2. Color-coded morphing process of the 3D geometry of the cortical surface

The still image illustrates how each vertex on the cortical surface morphs from an ancestry-neutral 3D cortical surface (a 25% proportion of genetic ancestry in all ancestral components) to a 3D cortical surface with a 100% proportion of genetic ancestry in a specific ancestral component. The morphing coefficients were estimated from the PING sample. Here, the colors represent the direction of the morphing process. Moving along the medial-lateral axis is coded in red, along the anterior-posterior axis in green, along the dorsal-ventral axis in blue. The final color is the combination of these three, depending on which direction the vertices move. For each viewing perspective, the coloring frame of reference is rendered on the top of each column. The length of each morphing line is the actual distance between two 3D cortical surfaces. For dynamic morphing animations, see movies S1 to S3 in the online materials.

Figure 3. Mean magnitude and variations of morphing across 12 regions of cortical surface

Labeled in the topmost images, the following regions are defined in a previous publication [17]: 1. central region, 2. occipital cortex, 3. posterolateral-temporal region, 4. superiorparietal region, 5. orbitofrontal region, 6. superiotemporal region, 7. inferiorparietal region, 8. dorsomedialfrontal region, 9. anteromedial-temporal region, 10. precuneus, 11. dorsolateral-prefrontal cortex, 12. parsopercularis. The Euclidean distances between cortical surface of 100% ancestry and neutral ancestry were calculated for each vertex. Depending on the surface regions where the vertices are situated, the mean and standard deviations of the Euclidean distances are shown in the box plots.