The head and facial features of different groups are significantly different, and are closely related to the origin, migration and evolution of humans. The facial morphology of East Asian and European populations is significantly different, what are the genetic factors behind this? Is there a natural selection effect?
In order to solve the above problems, the team of researcher Wang Sijia of the Shanghai Institute of Nutrition and Health of the Chinese Academy of Sciences and the team of Jin Li, academician of the Chinese Academy of Sciences and professor of Fudan University, conducted in-depth research on this in conjunction with scientific research institutions at home and abroad, and in the largest East Asian population data so far, the correlation analysis of head and face phenotype and genotype was carried out through a set of automatic quantification methods of human head and facial features based on image analysis and computer algorithms. From the perspective of heredity and evolution, the hot spots of human head and facial phenotypic differences are analyzed, the genetic mechanism of unique facial morphology in some East Asia is revealed, and the genetic factors causing Eurasian facial differences are also identified.
On the evening of April 7, 2022, Beijing time, the relevant research results were published in the international journal Nature (Nature) under the title of "Genetic variants underlying differences in facial morphology in East Asian and European populations" ("Genetic variants underlying differences in facial morphology in East Asian and European populations"). Genetics）。
This study optimizes phenotypic quantification and analyzes the genetic structure of east Asian faces. The pictures in this article are all courtesy of Fudan University
Analysis of the genetic structure of east Asian faces
Based on nearly 10,000 3D face images, the researchers first constructed a set of facial segmentation methods that combined anatomical information. The facial area is aggregated into 10 main structures, namely the forehead, the arch of the eyebrows, the eyes, the temporals, the cheeks, the nose, the cheeks, the upper and lower mouths, and the lower jaw. The posterior phenotype of the segment obtained in this way can perfectly correspond to the anatomical position, laying the foundation for subsequent genetic analysis.
The human head and face morphology is highly heritable, but what genetic mechanism regulates facial differences between populations? Using the multivariate typical correlation analysis, the researchers identified 244 genetic variants affecting the morphology of the head and face of east Asian groups, and confirmed that facial features as typical complex traits are influenced by multiple genes. Through collaboration with the European team, it was further discovered that the Eurasian differential signal may be functionally homogeneous, caused by frequency changes.
The study also found that the head and face related genes are mainly enriched in the enhancers of regulatory genes in the late stage of embryonic development, which are involved in skeletal phylogenetic development, regionalization pattern regulation, and tissue generation. Whole phenotypic group association analysis (PheWAS) found that related genetic loci that affect facial morphology also affect other human phenotypic features such as body composition, constitution, and hair.
It is worth mentioning that this study found that the facial morphological phenotype-related site rs6843082 is significantly associated with the risk of atrial fibrillation, and the related site has been reported to affect cardiogenic embolic stroke and ischemic stroke, which suggests that the facial feature phenotype may be associated with the risk of cardiovascular disease.
Innovative visual methods to show the characteristics of Eurasian facial differences
Compared with Europeans, East Asians have more prominent cheeks, eyebrow arches, noses and are more gentle. This genetic mechanism of facial differences between different groups of people has attracted many scholars to explore in depth.
In order to explore the genetic basis of key facial differences in Eurasian populations, the research team for the first time generalized the polygenic score (PGS) method to complex shape phenotypes, and innovatively proposed the Polygenic Shape Analysis (PSA) method, which provided a visual basis for the simulation of facial morphology.
The study found that the true facial morphology differences in different populations in Europe and Asia were highly consistent with the Eurasian characteristics influenced by genetic factors simulated by PSA, and 13 genetic factors related to the unique facial features of East Asia were identified. At the same time, the correlation sites are well in line with the East Asian origin/derivation guess in terms of both effect and generation time.
For example, rs8068343, as an independent site near SOX9, has a significant frequency difference between Europe and Asia, resulting in a more prominent genotype of the nose dominating in Europe, and the researchers speculate that this site is likely to cause nasal differences between Europe and Asia, while the remaining three sites near SOX9 affect more intra-population differences.
Integrated selection analysis to reveal nasal adaptive selection mechanisms
Using a variety of natural selection analysis methods, the study for the first time explored hotspots of facial selection from a genetic perspective, and found that Eurasian nose differences are likely due to adaptive selection in Europe and genetic drift in East Asia.
This conclusion reveals the mechanism of natural selection that causes differences in the shape of the facial nose of different groups, and suggests that researchers can analyze the ancient DNA and climate data in the next step, and correlate the evolution of the nose and brow arch morphology of the ancients with climate change, providing a new idea for the complexity and diversity evolution mechanism of the physical phenotype of the East Asian population.
Jin Li said that this achievement is another successful attempt to carry out life science research with phenotypic omics concepts, paradigms and methods in the process of promoting the human phenotypic group plan. For the first time, the potential genetic basis of facial phenotypic differences in different populations is elucidated, which greatly expands the knowledge of East Asian facial phenotypic genetics and is of great significance to the understanding of human beings themselves.
Zhang Manfei, postdoctoral fellow of the Institute of Human Phenotype Group of Fudan University, Wu Sijie, postdoctoral fellow of the School of Life Sciences of Fudan University, Du Siyuan, doctoral student of shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, and Qian Wei, postdoctoral fellow of the Institute of Human Phenotype Group of Fudan University, are the co-first authors of the paper, and Researcher Wang Sijia, Dr. Li Jiarui and Academician Jin Li are the co-corresponding authors of the paper.