IU Indianapolis ScholarWorks :: Browsing by Author "Weinberg, Seth M."

Browsing by Author "Weinberg, Seth M."

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3D facial phenotyping by biometric sibling matching used in contemporary genomic methodologies
(Public Library of Science, 2021-05-13) Hoskens, Hanne; Liu, Dongjing; Naqvi, Sahin; Lee, Myoung Keun; Eller, Ryan J.; Indencleef, Karlijne; White, Julie D.; Li, Jiarui; Larmuseau, Maarten H. D.; Hens, Greet; Wysocka, Joanna; Walsh, Susan; Richmond, Stephen; Shriver, Mark D.; Shaffer, John R.; Peeters, Hilde; Weinberg, Seth M.; Claes, Peter; Biology, School of Science
The analysis of contemporary genomic data typically operates on one-dimensional phenotypic measurements (e.g. standing height). Here we report on a data-driven, family-informed strategy to facial phenotyping that searches for biologically relevant traits and reduces multivariate 3D facial shape variability into amendable univariate measurements, while preserving its structurally complex nature. We performed a biometric identification of siblings in a sample of 424 children, defining 1,048 sib-shared facial traits. Subsequent quantification and analyses in an independent European cohort (n = 8,246) demonstrated significant heritability for a subset of traits (0.17-0.53) and highlighted 218 genome-wide significant loci (38 also study-wide) associated with facial variation shared by siblings. These loci showed preferential enrichment for active chromatin marks in cranial neural crest cells and embryonic craniofacial tissues and several regions harbor putative craniofacial genes, thereby enhancing our knowledge on the genetic architecture of normal-range facial variation.
Decoding the Human Face: Progress and Challenges in Understanding the Genetics of Craniofacial Morp
(Annual Reviews, 2022) Naqvi, Sahin; Hoskens, Hanne; Wilke, Franziska; Weinberg, Seth M.; Shaffer, John R.; Walsh, Susan; Shriver, Mark D.; Wysocka, Joanna; Claes, Peter; Biology, School of Science
Variations in the form of the human face, which plays a role in our individual identities and societal interactions, have fascinated scientists and artists alike. Here, we review our current understanding of the genetics underlying variation in craniofacial morphology and disease-associated dysmorphology, synthesizing decades of progress on Mendelian syndromes in addition to more recent results from genome-wide association studies of human facial shape and disease risk. We also discuss the various approaches used to phenotype and quantify facial shape, which are of particular importance due to the complex, multipartite nature of the craniofacial form. We close by discussing how experimental studies have contributed and will further contribute to our understanding of human genetic variation and then proposing future directions and applications for the field.
Effects of Male Facial Masculinity on Perceived Attractiveness
(Springer Nature, 2021) Ekrami, Omid; Claes, Peter; Shriver, Mark D.; Weinberg, Seth M.; Marazita, Mary L.; Walsh, Susan; Van Dongen, Stefan; Biology, School of Science
Studies suggest that high levels of masculinity in men can be a signal of 'better genes' as well as low parental investment. It is the trade-off between these two qualities that has led to the hypothesis that women's preferences for male masculinity are condition-dependent, yet, not all studies support this hypothesis. In addition, there is evidence that more average faces would be perceived as more attractive. Here we study the variation in masculinity preferences of a cohort of heterosexual women (n=769), using manipulated 3D faces of male subjects. We used linear mixed models to test for effects of various covariates such as relationship status, use of hormonal contraception, sociosexual orientation and self-perceived attractiveness on preference for masculinity. Our results show that women's sociosexual orientation has a positive correlation with masculinity preference while using hormonal contraception decreases this preference. None of the other covariates displayed any significant effect on masculinity preference. The initial level of masculinity of the faces (very low, low, average, high and very high) was also shown to affect this preference, where we found a significant preference for higher masculinity in the very low and average group, while no preference was found in the other groups. Our findings support the notion that condition-dependent variables have very small effects, if any, on women's preference for masculinity in men.
Exploring regional aspects of 3D facial variation within European individuals
(Springer Nature, 2023-03-06) Wilke, Franziska; Herrick, Noah; Matthews, Harold; Hoskens, Hanne; Singh, Sylvia; Shaffer, John R.; Weinberg, Seth M.; Shriver, Mark D.; Claes, Peter; Walsh, Susan; Biology, School of Science
Facial ancestry can be described as variation that exists in facial features that are shared amongst members of a population due to environmental and genetic effects. Even within Europe, faces vary among subregions and may lead to confounding in genetic association studies if unaccounted for. Genetic studies use genetic principal components (PCs) to describe facial ancestry to circumvent this issue. Yet the phenotypic effect of these genetic PCs on the face has yet to be described, and phenotype-based alternatives compared. In anthropological studies, consensus faces are utilized as they depict a phenotypic, not genetic, ancestry effect. In this study, we explored the effects of regional differences on facial ancestry in 744 Europeans using genetic and anthropological approaches. Both showed similar ancestry effects between subgroups, localized mainly to the forehead, nose, and chin. Consensus faces explained the variation seen in only the first three genetic PCs, differing more in magnitude than shape change. Here we show only minor differences between the two methods and discuss a combined approach as a possible alternative for facial scan correction that is less cohort dependent, more replicable, non-linear, and can be made open access for use across research groups, enhancing future studies in this field.
Fluctuating Asymmetry and Sexual Dimorphism in Human Facial Morphology: A Multi-Variate Study
(MDPI, 2021-02) Ekrami, Omid; Claes, Peter; Van Assche, Ellen; Shriver, Mark D.; Weinberg, Seth M.; Marazita, Mary L.; Walsh, Susan; Van Dongen, Stefan; Biology, School of Science
Background: Fluctuating asymmetry is often used as an indicator of developmental instability, and is proposed as a signal of genetic quality. The display of prominent masculine phenotypic features, which are a direct result of high androgen levels, is also believed to be a sign of genetic quality, as these hormones may act as immunosuppressants. Fluctuating asymmetry and masculinity are therefore expected to covary. However, there is lack of strong evidence in the literature regarding this hypothesis. Materials and methods: In this study, we examined a large dataset of high-density 3D facial scans of 1260 adults (630 males and 630 females). We mapped a high-density 3D facial mask onto the facial scans in order to obtain a high number of quasi-landmarks on the faces. Multi-dimensional measures of fluctuating asymmetry were extracted from the landmarks using Principal Component Analysis, and masculinity/femininity scores were obtained for each face using Partial Least Squares. The possible correlation between these two qualities was then examined using Pearson's coefficient and Canonical Correlation Analysis. Results: We found no correlation between fluctuating asymmetry and masculinity in men. However, a weak but significant correlation was found between average fluctuating asymmetry and masculinity in women, in which feminine faces had higher levels of fluctuating asymmetry on average. This correlation could possibly point to genetic quality as an underlying mechanism for both asymmetry and masculinity; however, it might also be driven by other fitness or life history traits, such as fertility. Conclusions: Our results question the idea that fluctuating asymmetry and masculinity should be (more strongly) correlated in men, which is in line with the recent literature. Future studies should possibly focus more on the evolutionary relevance of the observed correlation in women.
Genome scans of facial features in East Africans and cross-population comparisons reveal novel associations
(Public Library of Science, 2021-08-19) Liu, Chenxing; Lee, Myoung Keun; Naqvi, Sahin; Hoskens, Hanne; Liu, Dongjing; White, Julie D.; Indencleef, Karlijne; Matthews, Harold; Eller, Ryan J.; Li, Jiarui; Mohammed, Jaaved; Swigut, Tomek; Richmond, Stephen; Manyama, Mange; Hallgrímsson, Benedikt; Spritz, Richard A.; Feingold, Eleanor; Marazita, Mary L.; Wysocka, Joanna; Walsh, Susan; Shriver, Mark D.; Claes, Peter; Weinberg, Seth M.; Shaffer, John R.; Biology, School of Science
Facial morphology is highly variable, both within and among human populations, and a sizable portion of this variation is attributable to genetics. Previous genome scans have revealed more than 100 genetic loci associated with different aspects of normal-range facial variation. Most of these loci have been detected in Europeans, with few studies focusing on other ancestral groups. Consequently, the degree to which facial traits share a common genetic basis across diverse sets of humans remains largely unknown. We therefore investigated the genetic basis of facial morphology in an East African cohort. We applied an open-ended data-driven phenotyping approach to a sample of 2,595 3D facial images collected on Tanzanian children. This approach segments the face into hierarchically arranged, multivariate features that capture the shape variation after adjusting for age, sex, height, weight, facial size and population stratification. Genome scans of these multivariate shape phenotypes revealed significant (p < 2.5 × 10-8) signals at 20 loci, which were enriched for active chromatin elements in human cranial neural crest cells and embryonic craniofacial tissue, consistent with an early developmental origin of the facial variation. Two of these associations were in highly conserved regions showing craniofacial-specific enhancer activity during embryological development (5q31.1 and 12q21.31). Six of the 20 loci surpassed a stricter threshold accounting for multiple phenotypes with study-wide significance (p < 6.25 × 10-10). Cross-population comparisons indicated 10 association signals were shared with Europeans (seven sharing the same associated SNP), and facilitated fine-mapping of causal variants at previously reported loci. Taken together, these results may point to both shared and population-specific components to the genetic architecture of facial variation.
Insights into the genetic architecture of the human face
(Springer Nature, 2021) White, Julie D.; Indencleef, Karlijne; Naqvi, Sahin; Eller, Ryan J.; Hoskens, Hanne; Roosenboom, Jasmien; Lee, Myoung Keun; Li, Jiarui; Mohammed, Jaaved; Richmond, Stephen; Quillen, Ellen E.; Norton, Heather L.; Feingold, Eleanor; Swigut, Tomek; Marazita, Mary L.; Peeters, Hilde; Hens, Greet; Shaffer, John R.; Wysocka, Joanna; Walsh, Susan; Weinberg, Seth M.; Shriver, Mark D.; Claes, Peter; Biology, School of Science
The human face is complex and multipartite, and characterization of its genetic architecture remains challenging. Using a multivariate genome-wide association study meta-analysis of 8,246 European individuals, we identified 203 genome-wide-significant signals (120 also study-wide significant) associated with normal-range facial variation. Follow-up analyses indicate that the regions surrounding these signals are enriched for enhancer activity in cranial neural crest cells and craniofacial tissues, several regions harbor multiple signals with associations to different facial phenotypes, and there is evidence for potential coordinated actions of variants. In summary, our analyses provide insights into the understanding of how complex morphological traits are shaped by both individual and coordinated genetic actions.
Large-scale open-source three-dimensional growth curves for clinical facial assessment and objective description of facial dysmorphism
(Springer Nature, 2021-06-09) Matthews, Harold S.; Palmer, Richard L.; Baynam, Gareth S.; Quarrell, Oliver W.; Klein, Ophir D.; Spritz, Richard A.; Hennekam, Raoul C.; Walsh, Susan; Shriver, Mark; Weinberg, Seth M.; Hallgrimsson, Benedikt; Hammond, Peter; Penington, Anthony J.; Peeters, Hilde; Claes, Peter D.; Biology, School of Science
Craniofacial dysmorphism is associated with thousands of genetic and environmental disorders. Delineation of salient facial characteristics can guide clinicians towards a correct clinical diagnosis and understanding the pathogenesis of the disorder. Abnormal facial shape might require craniofacial surgical intervention, with the restoration of normal shape an important surgical outcome. Facial anthropometric growth curves or standards of single inter-landmark measurements have traditionally supported assessments of normal and abnormal facial shape, for both clinical and research applications. However, these fail to capture the full complexity of facial shape. With the increasing availability of 3D photographs, methods of assessment that take advantage of the rich information contained in such images are needed. In this article we derive and present open-source three-dimensional (3D) growth curves of the human face. These are sequences of age and sex-specific expected 3D facial shapes and statistical models of the variation around the expected shape, derived from 5443 3D images. We demonstrate the use of these growth curves for assessing patients and show that they identify normal and abnormal facial morphology independent from age-specific facial features. 3D growth curves can facilitate use of state-of-the-art 3D facial shape assessment by the broader clinical and biomedical research community. This advance in phenotype description will support clinical diagnosis and the understanding of disease pathogenesis including genotype–phenotype relations.
Mapping genes for human face shape: Exploration of univariate phenotyping strategies
(Public Library of Science, 2024-12-02) Yuan, Meng; Goovaerts, Seppe; Vanneste, Michiel; Matthews, Harold; Hoskens, Hanne; Richmond, Stephen; Klein, Ophir D.; Spritz, Richard A.; Hallgrimsson, Benedikt; Walsh, Susan; Shriver, Mark D.; Shaffer, John R.; Weinberg, Seth M.; Peeters, Hilde; Claes, Peter; Biology, School of Science
Human facial shape, while strongly heritable, involves both genetic and structural complexity, necessitating precise phenotyping for accurate assessment. Common phenotyping strategies include simplifying 3D facial features into univariate traits such as anthropometric measurements (e.g., inter-landmark distances), unsupervised dimensionality reductions (e.g., principal component analysis (PCA) and auto-encoder (AE) approaches), and assessing resemblance to particular facial gestalts (e.g., syndromic facial archetypes). This study provides a comparative assessment of these strategies in genome-wide association studies (GWASs) of 3D facial shape. Specifically, we investigated inter-landmark distances, PCA and AE-derived latent dimensions, and facial resemblance to random, extreme, and syndromic gestalts within a GWAS of 8,426 individuals of recent European ancestry. Inter-landmark distances exhibit the highest SNP-based heritability as estimated via LD score regression, followed by AE dimensions. Conversely, resemblance scores to extreme and syndromic facial gestalts display the lowest heritability, in line with expectations. Notably, the aggregation of multiple GWASs on facial resemblance to random gestalts reveals the highest number of independent genetic loci. This novel, easy-to-implement phenotyping approach holds significant promise for capturing genetically relevant morphological traits derived from complex biomedical imaging datasets, and its applications extend beyond faces. Nevertheless, these different phenotyping strategies capture different genetic influences on craniofacial shape. Thus, it remains valuable to explore these strategies individually and in combination to gain a more comprehensive understanding of the genetic factors underlying craniofacial shape and related traits.
A Multivariate Approach to Determine the Dimensionality of Human Facial Asymmetry
(MDPI, 2020-03) Ekrami, Omid; Claes, Peter; White, Julie D.; Weinberg, Seth M.; Marazita, Mary L.; Walsh, Susan; Shriver, Mark D.; Van Dongen, Stefan; Biology, School of Science
Many studies have suggested that developmental instability (DI) could lead to asymmetric development, otherwise known as fluctuating asymmetry (FA). Several attempts to unravel the biological meaning of FA have been made, yet the main step in estimating FA is to remove the effects of directional asymmetry (DA), which is defined as the average bilateral asymmetry at the population level. Here, we demonstrate in a multivariate context that the conventional method of DA correction does not adequately compensate for the effects of DA in other dimensions of asymmetry. This appears to be due to the presence of between-individual variation along the DA dimension. Consequently, we propose to decompose asymmetry into its different orthogonal dimensions, where we introduce a new measure of asymmetry, namely fluctuating directional asymmetry (F-DA). This measure describes individual variation in the dimension of DA, and can be used to adequately correct the asymmetry measurements for the presence of DA. We provide evidence that this measure can be useful in disentangling the different dimensions of asymmetry, and further studies on this measure can provide valuable insight into the underlying biological processes leading to these different asymmetry dimensions.

Browsing by Author "Weinberg, Seth M."

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