Jorge Gómez-Valdés

Admixture in Latin America: Geographic Structure, Phenotypic Diversity and Self-Perception of Ancestry Based on 7,342 Individuals

The current genetic makeup of Latin America has been shaped by a history of extensive admixture between Africans, Europeans and Native Americans, a process taking place within the context of extensive geographic and social stratification. We estimated individual ancestry proportions in a sample of 7,342 subjects ascertained in five countries (Brazil, Chile, Colombia, México and Perú). These individuals were also characterized for a range of physical appearance traits and for self-perception of ancestry. The geographic distribution of admixture proportions in this sample reveals extensive population structure, illustrating the continuing impact of demographic history on the genetic diversity of Latin America. Significant ancestry effects were detected for most phenotypes studied. However, ancestry generally explains only a modest proportion of total phenotypic variation. Genetically estimated and self-perceived ancestry correlate significantly, but certain physical attributes have a strong impact on self-perception and bias self-perception of ancestry relative to genetically estimated ancestry.

A genome-wide association scan implicates DCHS2 , RUNX2 , GLI3 , PAX1 and EDAR in human facial variation

We report a genome-wide association scan for facial features in ∼6,000 Latin Americans. We evaluated 14 traits on an ordinal scale and found significant association (P values<5 × 10−8) at single-nucleotide polymorphisms (SNPs) in four genomic regions for three nose-related traits: columella inclination (4q31), nose bridge breadth (6p21) and nose wing breadth (7p13 and 20p11). In a subsample of ∼3,000 individuals we obtained quantitative traits related to 9 of the ordinal phenotypes and, also, a measure of nasion position. Quantitative analyses confirmed the ordinal-based associations, identified SNPs in 2q12 associated to chin protrusion, and replicated the reported association of nasion position with SNPs in PAX3. Strongest association in 2q12, 4q31, 6p21 and 7p13 was observed for SNPs in the EDAR, DCHS2, RUNX2 and GLI3 genes, respectively. Associated SNPs in 20p11 extend to PAX1. Consistent with the effect of EDAR on chin protrusion, we documented alterations of mandible length in mice with modified Edar funtion.

Lack of support for the association between facial shape and aggression: a reappraisal based on a worldwide population genetics perspective.

Antisocial and criminal behaviors are multifactorial traits whose interpretation relies on multiple disciplines. Since these interpretations may have social, moral and legal implications, a constant review of the evidence is necessary before any scientific claim is considered as truth. A recent study proposed that men with wider faces relative to facial height (fWHR) are more likely to develop unethical behaviour mediated by a psychological sense of power. This research was based on reports suggesting that sexual dimorphism and selection would be responsible for a correlation between fWHR and aggression. Here we show that 4,960 individuals from 94 modern human populations belonging to a vast array of genetic and cultural contexts do not display significant amounts of fWHR sexual dimorphism. Further analyses using populations with associated ethnographical records as well as samples of male prisoners of the Mexico City Federal Penitentiary condemned by crimes of variable level of inter-personal aggression (homicide, robbery, and minor faults) did not show significant evidence, suggesting that populations/individuals with higher levels of bellicosity, aggressive behaviour, or power-mediated behaviour display greater fWHR. Finally, a regression analysis of fWHR on individuals fitness showed no significant correlation between this facial trait and reproductive success. Overall, our results suggest that facial attributes are poor predictors of aggressive behaviour, or at least, that sexual selection was weak enough to leave a signal on patterns of between- and within-sex and population facial variation.

A genome-wide association scan in admixed Latin Americans identifies loci influencing facial and scalp hair features

We report a genome-wide association scan in over 6,000 Latin Americans for features of scalp hair (shape, colour, greying, balding) and facial hair (beard thickness, monobrow, eyebrow thickness). We found 18 signals of association reaching genome-wide significance (P values 5 × 10−8 to 3 × 10−119), including 10 novel associations. These include novel loci for scalp hair shape and balding, and the first reported loci for hair greying, monobrow, eyebrow and beard thickness. A newly identified locus influencing hair shape includes a Q30R substitution in the Protease Serine S1 family member 53 (PRSS53). We demonstrate that this enzyme is highly expressed in the hair follicle, especially the inner root sheath, and that the Q30R substitution affects enzyme processing and secretion. The genome regions associated with hair features are enriched for signals of selection, consistent with proposals regarding the evolution of human hair.

Detection of a population replacement at the Classic–Postclassic transition in Mexico

The Mexica Empire reached an outstanding social, economic and politic organization among Mesoamerican civilizations. Even though archaeology and history provide substantial information about their past, their biological origin and the demographic consequences of their settlement in the Central Valley of Mexico remain unsolved. Two main hypotheses compete to explain the Mexica origin: a social reorganization of the groups already present in the Central Valley after the fall of the Classic centres or a population replacement of the Mesoamerican groups by migrants from the north and the consequent setting up of the Mexica society. Here, we show that the main changes in the facial phenotype occur during the Classic–Postclassic transition, rather than in the rise of the Mexica. Furthermore, Mexica facial morphology seems to be already present in the early phases of the Postclassic epoch and is not related to the northern facial pattern. A combination of geometric morphometrics with Relethford–Blangero analyses of within- versus among-group variation indicates that Postclassic groups are more variable than expected. This result suggests that intense gene exchange was likely after the fall of the Classic and maybe responsible for the Postclassic facial phenotype. The source population for the Postclassic groups could be located somewhere in western Mesoamerica, since North Mexico and Central Mesoamerican Preclassic and Classic groups are clearly divergent from the Postclassic ones. Similarity among Preclassic and Classic groups and those from Aridoamerica could be reflecting the ancestral phenotypic pattern characteristic of the groups that first settled Mesoamerica.

A genome-wide association study identifies multiple loci for variation in human ear morphology

Here we report a genome-wide association study for non-pathological pinna morphology in over 5,000 Latin Americans. We find genome-wide significant association at seven genomic regions affecting: lobe size and attachment, folding of antihelix, helix rolling, ear protrusion and antitragus size (linear regression P values 2 × 10−8 to 3 × 10−14). Four traits are associated with a functional variant in the Ectodysplasin A receptor (EDAR) gene, a key regulator of embryonic skin appendage development. We confirm expression of Edar in the developing mouse ear and that Edar-deficient mice have an abnormally shaped pinna. Two traits are associated with SNPs in a region overlapping the T-Box Protein 15 (TBX15) gene, a major determinant of mouse skeletal development. Strongest association in this region is observed for SNP rs17023457 located in an evolutionarily conserved binding site for the transcription factor Cartilage paired-class homeoprotein 1 (CART1), and we confirm that rs17023457 alters in vitro binding of CART1.

Comparison of methods to determine sex by evaluating the greater sciatic notch: Visual, angular and geometric morphometrics

Sex estimation is the first step for biological profile reconstruction of an unknown skeleton (archaeological or contemporary) and consequently for positive identification of skeletal remains recovered from forensic settings. Several tools have been developed using different osseous structures. With the intention to provide an objective method comparison, we reported the analysis of three different methods (visual, metric and geometric morphometrics) for sex assessment of the greater sciatic notch. One hundred and thirty pelvic bones (45.4% females and 54.6% males) from the National Autonomous University of Mexico Skeletal Collection pertaining to the contemporary Mexican population were analyzed. We used the ROC-analysis to test between desired false positive thresholds (1-specificity) and expected true positive rates (sensitivity) in order to predict the best approach to sex assessment. The comparison of the area under the ROC-curves shows significant differences among visual and metric methods. At the same time, the analysis suggested that higher morphological variation among the sexes is independent of the methodological approach. The results indicate that the metric (angle), with a high percent of indeterminate cases (34.6%), and visual, with 26.2% of the cases allocated as intermediate cases, were poorly accurate; we cannot recommend these techniques for sexing an unknown specimen. On the other hand, the geometric morphometrics approach improves sex estimation in 82.3% of correctly classified individuals with more than 95% of posterior probability. In addition to the method comparison, the major sexual variation of the greater sciatic notch was determined to be located on its posterior border.

Technical Note: Geometric Morphometrics and Sexual Dimorphism of the Greater Sciatic Notch in Adults From Two Skeletal Collections: The Accuracy and Reliability of Sex Classification

The greater sciatic notch (GSN) is one of the most important and frequently used characteristics for determining the sex of skeletons, but objective assessment of this characteristic is not without its difficulties. We tested the robustness of GSN sex classification on the basis of geometric morphometrics (GM) and support vector machines (SVM), using two different population samples. Using photographs, the shape of the GSN in 229 samples from two assemblages (documented collections of a Euroamerican population from the Maxwell Museum, University of New Mexico, and a Hispanic population from Universidad Nacional Autónoma de México, Mexico City) was segmented automatically and evaluated using six curve representations. The optimal dimensionality for each representation was determined by finding the best sex classification. The classification accuracy of the six curve representations in our study was similar but the highest and concurrently homologous cross-validated accuracy of 92% was achieved for a pooled sample using Fourier coefficient and Legendre polynomial methods. The success rate of our classification was influenced by the number of semilandmarks or coefficients and was only slightly affected by GSN marginal point positions. The intrapopulation variability of the female GSN shape was significantly lower compared with the male variability, possibly as a consequence of the intense selection pressure associated with reproduction. Males were misclassified more often than females. Our results show that by using a suitable GSN curve representation, a GM approach, and SVM analysis, it is possible to obtain a robust separation between the sexes that is stable for a multipopulation sample.

Facial asymmetry and genetic ancestry in Latin American admixed populations

Fluctuating and directional asymmetry are aspects of morphological variation widely used to infer environmental and genetic factors affecting facial phenotypes. However, the genetic basis and environmental determinants of both asymmetry types is far from being completely known. The analysis of facial asymmetries in admixed individuals can be of help to characterize the impact of a genomes heterozygosity on the developmental basis of both fluctuating and directional asymmetries. Here we characterize the association between genetic ancestry and individual asymmetry on a sample of Latin-American admixed populations. To do so, three-dimensional (3D) facial shape attributes were explored on a sample of 4,104 volunteers aged between 18 and 85 years. Individual ancestry and heterozygosity was estimated using more than 730,000 genome-wide markers. Multivariate techniques applied to geometric morphometric data were used to evaluate the magnitude and significance of directional and fluctuating asymmetry (FA), as well as correlations and multiple regressions aimed to estimate the relationship between facial FA scores and heterozygosity and a set of covariates. Results indicate that directional and FA are both significant, the former being the strongest expression of asymmetry in this sample. In addition, our analyses suggest that there are some specific patterns of facial asymmetries characterizing the different ancestry groups. Finally, we find that more heterozygous individuals exhibit lower levels of asymmetry. Our results highlight the importance of including ancestry-admixture estimators, especially when the analyses are aimed to compare levels of asymmetries on groups differing on socioeconomic levels, as a proxy to estimate developmental noise.

FGFR1 signaling is associated with the magnitude of morphological integration in human head shape

The head can be used as a model to study complex phenotypes controlled simultaneously by morphological integration (MI) due to common factors, and modular patterns caused by local factors affecting the development and functional demands of specific structures. The fibroblast growth factor and receptor system (FGF/FGFR) participates in cell communication and pattern formation in osseous tissues, among others, and there is compelling evidence from mouse model studies suggesting a role of the FGF/FGFR pathway as a covariance‐generating signaling process in head development. Here we use human data to test if specific genetic variants of another gene of this pathway, the FGFR1 gene, can be associated with differences in the integration of the head.