Predictors of Quality of Work Life in Health Care Workers at Adult Critical Care Units: A Cross-sectional Study.

Aim and background: Satisfaction with the quality of work life reflects the inadequate distribution of the workforce in critical care units and is not enough; on many occasions, they work in precarious conditions and with high levels of physical, emotional, spiritual, and social demands, impacting the quality of care. Aim: To identify predictors of the quality of work life of healthcare workers in adult critical care units (ACCU). Materials and methods: Quantitative study, cross-sectional analytical design with stratified two-stage sampling; three instruments were applied to 209 healthcare professionals in adult critical care units in different sites in a region of Colombia, concerning Quality of Life at Work-GOHISALO, Copenhagen Psychosocial Questionnaire-COPSOQ and Professional Quality of Life-ProQoL V. Multiple ordinal logistic regression was performed with exposure variables from the COPSOQ and ProQoL domains; the outcome variables were the dimensions of the Quality of Work Life instrument. Ethical standards for research involving human subjects were ensured. Results: According to the results of the multiple logistic models, quality of work life is predicted by job integration and predictability (OR = 6.93; 95% CI = 3.6-13.9), leisure time management and double presence (OR = 4.5; 95% CI = 1.22-8.79). Both job satisfaction and job security are related to leadership quality (OR=3.82; 95% CI = 2.27-6.55 and OR = 3.18; 95% CI = 1.22-8.79), respectively. Conclusions: The quality of work life of healthcare workers in adult intensive care units is predicted by quantitative demands, double presence, emotional demands, work pace, predictability, vertical trust, and quality of leadership. How to cite this article: Quinones-Rozo LP, Canaval-Erazo GE, Sandoval-Moreno LM. Predictors of Quality of Work Life in Health Care Workers at Adult Critical Care Units: A Cross-sectional Study. Indian J Crit Care Med 2024;28(4):355-363.

[Deaths from traffic injuries and social inequality in Colombia, 2019Mortalidade por acidentes de trânsito e desigualdades sociais na Colômbia, 2019]. / Mortalidad por lesiones de tránsito y desigualdades sociales en Colombia, 2019.

Objective: To evaluate the association between social inequalities and deaths from traffic injuries in Colombia in 2019. Methods: This ecological study evaluated the association between social inequalities and deaths from traffic injuries among users of the road transport system in Colombia in 2019, based on secondary information sources, using the department level as the administrative and geographic unit of study. A descriptive statistical analysis of health indicators and equity stratifiers was performed. Absolute and relative measures were used to determine social inequality gaps. Results: In 2019, 6 580 people died from road traffic injuries in Colombia. The majority of them (82%) were men. The most critical user condition was being a motorcyclist. The age group with the most victims was approximately 30 years old. Departments with populations between 500 000 and 2 000 000 were the most represented. The most critical equity stratifier was the number of registered motorcycles per 100 000 population. Significant inequality gaps between departments were observed. Conclusions: Inequalities in deaths from road traffic injuries in Colombia were observed. Policies and actions should focus on helping to reduce identified inequities, resulting in better quality of life, well-being, and health for the population.

Objetivo: Avaliar a relação entre desigualdades sociais e mortalidade por acidentes de trânsito na Colômbia no ano de 2019. Métodos: Este estudo ecológico avaliou a relação entre desigualdades sociais e mortalidade por acidentes de trânsito entre usuários do sistema de transporte rodoviário na Colômbia em 2019, com base em fontes secundárias de informação e departamentos como unidades administrativas e geográficas do estudo. Foi feita uma análise estatística descritiva do indicador de saúde e dos estratificadores de equidade, e foram utilizadas medidas absolutas e relativas para determinar as lacunas de desigualdade social. Resultados: Em 2019, 6 580 pessoas morreram na Colômbia em decorrência de acidentes de trânsito, em sua maioria homens (82%). A categoria de usuário mais afetada foi a de motociclistas, e a faixa etária com o maior número de vítimas girava em torno dos 30 anos. Departamentos com população entre 500 mil e 2 milhões de habitantes tiveram a maior participação. O estratificador de equidade com a condição mais crítica de desigualdade foi o número de motocicletas registradas por 100 mil habitantes. Foram evidenciadas lacunas significativas de desigualdade entre os departamentos. Conclusões: Foram reconhecidas desigualdades na mortalidade por acidentes de trânsito na Colômbia. É preciso implementar políticas e ações que contribuam para a redução das desigualdades identificadas, o que resultará em qualidade de vida, bem-estar e saúde para os cidadãos.

Mortalidad por lesiones de tránsito y desigualdades sociales en Colombia, 2019

[RESUMEN]. Objetivo. Evaluar la asociación entre las desigualdades sociales y la mortalidad por lesiones de tránsito en Colombia durante 2019. Métodos. En este estudio ecológico se evaluó la asociación entre las desigualdades sociales y la mortalidad por lesiones de tránsito de las personas usuarias del sistema de transporte terrestre carretero en Colombia durante 2019, con base en fuentes secundarias de información, a nivel de departamento como unidad admi- nistrativa y geográfica de estudio. Se hizo un análisis estadístico descriptivo tanto del indicador de salud como de los estratificadores de equidad y se utilizaron medidas absolutas y relativas para determinar las brechas de desigualdad social. Resultados. En 2019 murieron en Colombia 6 580 personas por lesiones de tránsito, la mayoría de las cuales (82%) eran hombres. La condición de usuario más crítica fue la de motociclista. El grupo etario con más víctimas tenía aproximadamente 30 años. Los departamentos con población entre 500 000 y 2 000 000 de habitantes tuvieron la más alta participación. El estratificador de equidad con la condición más crítica de des- igualdad fue el número de motocicletas registradas por cada 100 000 habitantes. Se evidenciaron brechas de desigualdad importantes entre los departamentos. Conclusiones. Se reconocieron desigualdades de la mortalidad por lesiones de tránsito en Colombia. Se deben orientar políticas y actuaciones que contribuyan a la disminución de las inequidades identificadas, lo que redunda en la calidad de vida, bienestar y salud de los ciudadanos.

[ABSTRACT]. Objective. To evaluate the association between social inequalities and deaths from traffic injuries in Colombia in 2019. Methods. This ecological study evaluated the association between social inequalities and deaths from traffic injuries among users of the road transport system in Colombia in 2019, based on secondary information sources, using the department level as the administrative and geographic unit of study. A descriptive statistical analysis of health indicators and equity stratifiers was performed. Absolute and relative measures were used to determine social inequality gaps. Results. In 2019, 6 580 people died from road traffic injuries in Colombia. The majority of them (82%) were men. The most critical user condition was being a motorcyclist. The age group with the most victims was approximately 30 years old. Departments with populations between 500 000 and 2 000 000 were the most represented. The most critical equity stratifier was the number of registered motorcycles per 100 000 popula- tion. Significant inequality gaps between departments were observed. Conclusions. Inequalities in deaths from road traffic injuries in Colombia were observed. Policies and actions should focus on helping to reduce identified inequities, resulting in better quality of life, well-being, and health for the population.

[RESUMO]. Objetivo. Avaliar a relação entre desigualdades sociais e mortalidade por acidentes de trânsito na Colômbia no ano de 2019. Métodos. Este estudo ecológico avaliou a relação entre desigualdades sociais e mortalidade por acidentes de trânsito entre usuários do sistema de transporte rodoviário na Colômbia em 2019, com base em fontes secundárias de informação e departamentos como unidades administrativas e geográficas do estudo. Foi feita uma análise estatística descritiva do indicador de saúde e dos estratificadores de equidade, e foram utilizadas medidas absolutas e relativas para determinar as lacunas de desigualdade social. Resultados. Em 2019, 6 580 pessoas morreram na Colômbia em decorrência de acidentes de trânsito, em sua maioria homens (82%). A categoria de usuário mais afetada foi a de motociclistas, e a faixa etária com o maior número de vítimas girava em torno dos 30 anos. Departamentos com população entre 500 mil e 2 milhões de habitantes tiveram a maior participação. O estratificador de equidade com a condição mais crítica de desigualdade foi o número de motocicletas registradas por 100 mil habitantes. Foram evidenciadas lacunas significativas de desigualdade entre os departamentos. Conclusões. Foram reconhecidas desigualdades na mortalidade por acidentes de trânsito na Colômbia. É preciso implementar políticas e ações que contribuam para a redução das desigualdades identificadas, o que resultará em qualidade de vida, bem-estar e saúde para os cidadãos.

Mortalidad por lesiones de tránsito y desigualdades sociales en Colombia, 2019 / Deaths from traffic injuries and social inequality in Colombia, 2019 / Mortalidade por acidentes de trânsito e desigualdades sociais na Colômbia, 2019

RESUMEN Objetivo. Evaluar la asociación entre las desigualdades sociales y la mortalidad por lesiones de tránsito en Colombia durante 2019. Métodos. En este estudio ecológico se evaluó la asociación entre las desigualdades sociales y la mortalidad por lesiones de tránsito de las personas usuarias del sistema de transporte terrestre carretero en Colombia durante 2019, con base en fuentes secundarias de información, a nivel de departamento como unidad administrativa y geográfica de estudio. Se hizo un análisis estadístico descriptivo tanto del indicador de salud como de los estratificadores de equidad y se utilizaron medidas absolutas y relativas para determinar las brechas de desigualdad social. Resultados. En 2019 murieron en Colombia 6 580 personas por lesiones de tránsito, la mayoría de las cuales (82%) eran hombres. La condición de usuario más crítica fue la de motociclista. El grupo etario con más víctimas tenía aproximadamente 30 años. Los departamentos con población entre 500 000 y 2 000 000 de habitantes tuvieron la más alta participación. El estratificador de equidad con la condición más crítica de desigualdad fue el número de motocicletas registradas por cada 100 000 habitantes. Se evidenciaron brechas de desigualdad importantes entre los departamentos. Conclusiones. Se reconocieron desigualdades de la mortalidad por lesiones de tránsito en Colombia. Se deben orientar políticas y actuaciones que contribuyan a la disminución de las inequidades identificadas, lo que redunda en la calidad de vida, bienestar y salud de los ciudadanos.

ABSTRACT Objective. To evaluate the association between social inequalities and deaths from traffic injuries in Colombia in 2019. Methods. This ecological study evaluated the association between social inequalities and deaths from traffic injuries among users of the road transport system in Colombia in 2019, based on secondary information sources, using the department level as the administrative and geographic unit of study. A descriptive statistical analysis of health indicators and equity stratifiers was performed. Absolute and relative measures were used to determine social inequality gaps. Results. In 2019, 6 580 people died from road traffic injuries in Colombia. The majority of them (82%) were men. The most critical user condition was being a motorcyclist. The age group with the most victims was approximately 30 years old. Departments with populations between 500 000 and 2 000 000 were the most represented. The most critical equity stratifier was the number of registered motorcycles per 100 000 population. Significant inequality gaps between departments were observed. Conclusions. Inequalities in deaths from road traffic injuries in Colombia were observed. Policies and actions should focus on helping to reduce identified inequities, resulting in better quality of life, well-being, and health for the population.

RESUMO Objetivo. Avaliar a relação entre desigualdades sociais e mortalidade por acidentes de trânsito na Colômbia no ano de 2019. Métodos. Este estudo ecológico avaliou a relação entre desigualdades sociais e mortalidade por acidentes de trânsito entre usuários do sistema de transporte rodoviário na Colômbia em 2019, com base em fontes secundárias de informação e departamentos como unidades administrativas e geográficas do estudo. Foi feita uma análise estatística descritiva do indicador de saúde e dos estratificadores de equidade, e foram utilizadas medidas absolutas e relativas para determinar as lacunas de desigualdade social. Resultados. Em 2019, 6 580 pessoas morreram na Colômbia em decorrência de acidentes de trânsito, em sua maioria homens (82%). A categoria de usuário mais afetada foi a de motociclistas, e a faixa etária com o maior número de vítimas girava em torno dos 30 anos. Departamentos com população entre 500 mil e 2 milhões de habitantes tiveram a maior participação. O estratificador de equidade com a condição mais crítica de desigualdade foi o número de motocicletas registradas por 100 mil habitantes. Foram evidenciadas lacunas significativas de desigualdade entre os departamentos. Conclusões. Foram reconhecidas desigualdades na mortalidade por acidentes de trânsito na Colômbia. É preciso implementar políticas e ações que contribuam para a redução das desigualdades identificadas, o que resultará em qualidade de vida, bem-estar e saúde para os cidadãos.

PRICKLE1 × FOCAD Interaction Revealed by Genome-Wide vQTL Analysis of Human Facial Traits.

The human face is a highly complex and variable structure resulting from the intricate coordination of numerous genetic and non-genetic factors. Hundreds of genomic loci impacting quantitative facial features have been identified. While these associations have been shown to influence morphology by altering the mean size and shape of facial measures, their effect on trait variance remains unclear. We conducted a genome-wide association analysis for the variance of 20 quantitative facial measurements in 2,447 European individuals and identified several suggestive variance quantitative trait loci (vQTLs). These vQTLs guided us to conduct an efficient search for gene-by-gene (G × G) interactions, which uncovered an interaction between PRICKLE1 and FOCAD affecting cranial base width. We replicated this G × G interaction signal at the locus level in an additional 5,128 Korean individuals. We used the hypomorphic Prickle1 Beetlejuice (Prickle1 Bj ) mouse line to directly test the function of Prickle1 on the cranial base and observed wider cranial bases in Prickle1 Bj/Bj . Importantly, we observed that the Prickle1 and Focadhesin proteins co-localize in murine cranial base chondrocytes, and this co-localization is abnormal in the Prickle1 Bj/Bj mutants. Taken together, our findings uncovered a novel G × G interaction effect in humans with strong support from both epidemiological and molecular studies. These results highlight the potential of studying measures of phenotypic variability in gene mapping studies of facial morphology.

The Influence of Sex and Ancestry on Three-Dimensional Palate Shape.

ABSTRACT: Modern human palate shape has been reported to vary by sex and ancestry, but limitations in the methods used to quantify shape and in population coverage have led to inconsistent findings. In the present study, the authors aim to characterize the effects of sex and ancestry on normal-range three-dimensional palate shape through landmark-based morphometrics.Three-dimensional digital dental casts were obtained and landmarked from 794 adults of European (n = 429), African (n = 295), and East Asian (n = 70) ancestry. Principal component analysis was conducted to identify patterns of shape variation present in our cohort, and canonical variates analysis was performed to test for shape differences between sexes and ancestries.Principal component analysis showed that 3 principal components, explaining 76.52% of variance, linked higher palatal vault with either a relative reduction in anteroposterior or mediolateral dimensions. Canonical variates analysis showed that males had wider and shorter palates with more posteriorly located maximum vault depth than females. Individuals of African ancestry, having higher vaults with more posteriorly located maximal depths, also had wider and shorter palates, whereas individuals of European ancestry had narrower and longer palates with more anteriorly located maximum vault depths. Individuals of East Asian ancestry showed the shallowest vaults.It was found that both sex and ancestry influence palate shape, suggesting a possible genetic component underlying this variation. Additionally, our findings indicate that vault height tends to co-vary with anteroposterior or mediolateral dimensions. Further investigation of these morphological patterns may shed light on possible links to common congenital anomalies such as orofacial clefting.

Impact of low-frequency coding variants on human facial shape.

The contribution of low-frequency variants to the genetic architecture of normal-range facial traits is unknown. We studied the influence of low-frequency coding variants (MAF < 1%) in 8091 genes on multi-dimensional facial shape phenotypes in a European cohort of 2329 healthy individuals. Using three-dimensional images, we partitioned the full face into 31 hierarchically arranged segments to model facial morphology at multiple levels, and generated multi-dimensional phenotypes representing the shape variation within each segment. We used MultiSKAT, a multivariate kernel regression approach to scan the exome for face-associated low-frequency variants in a gene-based manner. After accounting for multiple tests, seven genes (AR, CARS2, FTSJ1, HFE, LTB4R, TELO2, NECTIN1) were significantly associated with shape variation of the cheek, chin, nose and mouth areas. These genes displayed a wide range of phenotypic effects, with some impacting the full face and others affecting localized regions. The missense variant rs142863092 in NECTIN1 had a significant effect on chin morphology and was predicted bioinformatically to have a deleterious effect on protein function. Notably, NECTIN1 is an established craniofacial gene that underlies a human syndrome that includes a mandibular phenotype. We further showed that nectin1a mutations can affect zebrafish craniofacial development, with the size and shape of the mandibular cartilage altered in mutant animals. Findings from this study expanded our understanding of the genetic basis of normal-range facial shape by highlighting the role of low-frequency coding variants in several novel genes.

Parents of Children With Nonsyndromic Orofacial Clefting Show Altered Palate Shape.

OBJECTIVE: The unaffected relatives of individuals with nonsyndromic orofacial clefts have been shown to exhibit subtle craniofacial differences compared with the general population. Here, we investigate whether these morphological differences extend to the shape of the palate. DESIGN: We conducted a geometric morphometric analysis to compare palate shape in the clinically unaffected parents of children with nonsyndromic cleft lip with or without cleft palate and adult controls of European, Asian, and African ancestry. We conducted pairwise group comparisons using canonical variates analysis, and then confirmed and characterized findings of shape differences using Euclidean distance matrix analysis. RESULTS: Significant differences in palate shape were detected in unaffected mothers (but not fathers) compared to demographically matched controls. The differences in shape were ancestry-specific; mothers of Asian-derived and African-derived ancestry showed wider and shorter palates with higher posterior palatal vaults, while mothers of European-derived ancestry showed narrower palates with higher anterior palatal vaults. CONCLUSIONS: Our findings suggest that altered palate shape is a subclinical phenotypic feature, which may be indicative of elevated orofacial cleft risk. The risk phenotype varied by sex and ancestry, suggesting possible etiologic heterogeneity among demographic groups. Understanding the genetic basis of these informative palate shape traits may reveal new genes and pathways relevant to nonsyndromic orofacial clefting.

Prevalence of Torus Palatinus and association with dental arch shape in a multi-ethnic cohort.

Objectives: Torus Palatinus (TP) is a bony projection located on the oral surface of the hard palate. The trait is typically benign, has an unknown etiology, and varies widely in phenotypic expression. Prior studies suggest differences in TP prevalence by sex and ancestry, but the reported rates vary, even within a single ancestral group. We assessed the prevalence of TP and its association with palatal shape in a large multi-ethnic cohort of normal individuals. Methodology: 1102 adults were included (625 with European ancestry, 377 with West African anscestry, and 100 with East Asian ancestry). 3D digital dental casts were obtained and rated. TP frequencies were compared between sexes and/or ethnicities using Chi-squared tests. Dental cast models were then landmarked, and canonical variates analysis was performed to test for shape differences between those with and without TP. Results: Females had a significantly higher rate of TP than males across all three ancestral groups (p≤0.004). In males, no significant differences were found among ethnicities. Ancestral differences in TP frequency were driven by females, with East Asians having the highest rate (34.69%), followed by Europeans (24.88%) and West Africans (15.22%). Shape differences were found only in Asians and Africans, indicated a shorter and wider palate in presence of TP. Conclusions: Ethnic differences in TP frequency were present only in females. Further, females have considerably higher rates of TP than males in each population tested. Further studies of TP at earlier time-points and in connection to other aspects of craniofacial growth may shed light on these sex and ethnic differences.

Dataset of thermal and visible aerial images for multi-modal and multi-spectral image registration and fusion.

This article presents a dataset of thermal and visible aerial images of the same flat scene at Melendez campus of Universidad del Valle, Cali, Colombia. The images were acquired using an UAV equipped with either a thermal or a visible camera. The dataset is useful for testing techniques for the improvement, registration and fusion of multi-modal and multi-spectral images. The dataset consists of 30 visible images and their metadata, 80 thermal images and their metadata, and a visible georeferenced orthoimage. The metadata related to every image contains the WGS84 coordinates for allocating the images. Also, the homography matrices between every image and the orthoimage are included in the dataset. The images and homographies are compatible with the well-known assessment protocol for detection and description proposed by Mikolajczyk and Schmid [1].

Whole genome sequencing of orofacial cleft trios from the Gabriella Miller Kids First Pediatric Research Consortium identifies a new locus on chromosome 21.

Orofacial clefts (OFCs) are among the most prevalent craniofacial birth defects worldwide and create a significant public health burden. The majority of OFCs are non-syndromic, and the genetic etiology of non-syndromic OFCs is only partially determined. Here, we analyze whole genome sequence (WGS) data for association with risk of OFCs in European and Colombian families selected from a multicenter family-based OFC study. This is the first large-scale WGS study of OFC in parent-offspring trios, and a part of the Gabriella Miller Kids First Pediatric Research Program created for the study of childhood cancers and structural birth defects. WGS provides deeper and more specific genetic data than using imputation on present-day single nucleotide polymorphic (SNP) marker panels. Genotypes of case-parent trios at single nucleotide variants (SNV) and short insertions and deletions (indels) spanning the entire genome were called from their sequences using human GRCh38 genome assembly, and analyzed for association using the transmission disequilibrium test. Among genome-wide significant associations, we identified a new locus on chromosome 21 in Colombian families, not previously observed in other larger OFC samples of Latin American ancestry. This locus is situated within a region known to be expressed during craniofacial development. Based on deeper investigation of this locus, we concluded that it contributed risk for OFCs exclusively in the Colombians. This study reinforces the ancestry differences seen in the genetic etiology of OFCs, and underscores the need for larger samples when studying for OFCs and other birth defects in populations with diverse ancestry.

A systematic genetic analysis and visualization of phenotypic heterogeneity among orofacial cleft GWAS signals.

Phenotypic heterogeneity is a hallmark of complex traits, and genetic studies of such traits may focus on them as a single diagnostic entity or by analyzing specific components. For example, in orofacial clefting (OFC), three subtypes-cleft lip (CL), cleft lip and palate (CLP), and cleft palate (CP) have been studied separately and in combination. To further dissect the genetic architecture of OFCs and how a given associated locus may be contributing to distinct subtypes of a trait we developed a framework for quantifying and interpreting evidence of subtype-specific or shared genetic effects in complex traits. We applied this technique to create a "cleft map" of the association of 30 genetic loci with three OFC subtypes. In addition to new associations, we found loci with subtype-specific effects (e.g., GRHL3 [CP], WNT5A [CLP]), as well as loci associated with two or all three subtypes. We cross-referenced these results with mouse craniofacial gene expression datasets, which identified additional promising candidate genes. However, we found no strong correlation between OFC subtypes and expression patterns. In aggregate, the cleft map revealed that neither subtype-specific nor shared genetic effects operate in isolation in OFC architecture. Our approach can be easily applied to any complex trait with distinct phenotypic subgroups.

SNPs Associated With Testosterone Levels Influence Human Facial Morphology.

Many factors influence human facial morphology, including genetics, age, nutrition, biomechanical forces, and endocrine factors. Moreover, facial features clearly differ between males and females, and these differences are driven primarily by the influence of sex hormones during growth and development. Specific genetic variants are known to influence circulating sex hormone levels in humans, which we hypothesize, in turn, affect facial features. In this study, we investigated the effects of testosterone-related genetic variants on facial morphology. We tested 32 genetic variants across 22 candidate genes related to levels of testosterone, sex hormone-binding globulin (SHGB) and dehydroepiandrosterone sulfate (DHEAS) in three cohorts of healthy individuals for which 3D facial surface images were available (Pittsburgh 3DFN, Penn State and ALSPAC cohorts; total n = 7418). Facial shape was described using a recently developed extension of the dense-surface correspondence approach, in which the 3D facial surface was partitioned into a set of 63 hierarchically organized modules. Each variant was tested against each of the facial surface modules in a multivariate genetic association-testing framework and meta-analyzed. Additionally, the association between these candidate SNPs and five facial ratios was investigated in the Pittsburgh 3DFN cohort. Two significant associations involving intronic variants of SHBG were found: both rs12150660 (p = 1.07E-07) and rs1799941 (p = 6.15E-06) showed an effect on mandible shape. Rs8023580 (an intronic variant of NR2F2-AS1) showed an association with the total and upper facial width to height ratios (p = 9.61E-04 and p = 7.35E-04, respectively). These results indicate that testosterone-related genetic variants affect normal-range facial morphology, and in particular, facial features known to exhibit strong sexual dimorphism in humans.

Multiethnic GWAS Reveals Polygenic Architecture of Earlobe Attachment.

The genetic basis of earlobe attachment has been a matter of debate since the early 20th century, such that geneticists argue both for and against polygenic inheritance. Recent genetic studies have identified a few loci associated with the trait, but large-scale analyses are still lacking. Here, we performed a genome-wide association study of lobe attachment in a multiethnic sample of 74,660 individuals from four cohorts (three with the trait scored by an expert rater and one with the trait self-reported). Meta-analysis of the three expert-rater-scored cohorts revealed six associated loci harboring numerous candidate genes, including EDAR, SP5, MRPS22, ADGRG6 (GPR126), KIAA1217, and PAX9. The large self-reported 23andMe cohort recapitulated each of these six loci. Moreover, meta-analysis across all four cohorts revealed a total of 49 significant (p < 5 × 10-8) loci. Annotation and enrichment analyses of these 49 loci showed strong evidence of genes involved in ear development and syndromes with auricular phenotypes. RNA sequencing data from both human fetal ear and mouse second branchial arch tissue confirmed that genes located among associated loci showed evidence of expression. These results provide strong evidence for the polygenic nature of earlobe attachment and offer insights into the biological basis of normal and abnormal ear development.

Hypertelorism and Orofacial Clefting Revisited: An Anthropometric Investigation.

OBJECTIVE: Since the 1960s, multiple studies have reported a tendency toward hypertelorism in individuals with nonsyndromic orofacial clefts (OFCs). However, the association between specific cleft types and increased interorbital distance has been inconsistent. Using three-dimensional (3D) surface imaging, we tested whether different forms of clefting showed evidence of increased interorbital distance. METHODS: Intercanthal and outercanthal distances and intercanthal indices were calculated from 3D facial surface images of 287 individuals with repaired OFCs. Raw measurements were converted to sex and age-normalized Z-scores. Mean Z-scores for individuals with cleft lip (CL), cleft lip and palate (CLP), and cleft palate (CP) were compared with reference normative values (controls) and one another directly using t tests and analysis of variance. RESULTS: The CLP group showed a significant increase in intercanthal width (P = .001) and intercanthal index (P < .001) compared with reference norms. The CP group showed a significant decrease (P < .001) in outercanthal width. The CL group showed no difference from reference norms. The proportion of clinically hyperteloric individuals was generally low but highest in the CLP group (7.4%). Cleft severity had little effect on interorbital spacing. CONCLUSIONS: Individuals with CLP exhibited on average a tendency toward mild hypertelorism, driven primarily by an increase in intercanthal distance. This tendency was not seen in CL or CP.

Genome-Wide Association Study Reveals Multiple Loci Influencing Normal Human Facial Morphology.

Numerous lines of evidence point to a genetic basis for facial morphology in humans, yet little is known about how specific genetic variants relate to the phenotypic expression of many common facial features. We conducted genome-wide association meta-analyses of 20 quantitative facial measurements derived from the 3D surface images of 3118 healthy individuals of European ancestry belonging to two US cohorts. Analyses were performed on just under one million genotyped SNPs (Illumina OmniExpress+Exome v1.2 array) imputed to the 1000 Genomes reference panel (Phase 3). We observed genome-wide significant associations (p < 5 x 10-8) for cranial base width at 14q21.1 and 20q12, intercanthal width at 1p13.3 and Xq13.2, nasal width at 20p11.22, nasal ala length at 14q11.2, and upper facial depth at 11q22.1. Several genes in the associated regions are known to play roles in craniofacial development or in syndromes affecting the face: MAFB, PAX9, MIPOL1, ALX3, HDAC8, and PAX1. We also tested genotype-phenotype associations reported in two previous genome-wide studies and found evidence of replication for nasal ala length and SNPs in CACNA2D3 and PRDM16. These results provide further evidence that common variants in regions harboring genes of known craniofacial function contribute to normal variation in human facial features. Improved understanding of the genes associated with facial morphology in healthy individuals can provide insights into the pathways and mechanisms controlling normal and abnormal facial morphogenesis.

Passive Smoke Exposure as a Risk Factor for Oral Clefts-A Large International Population-Based Study.

Maternal cigarette smoking is a well-established risk factor for oral clefts. Evidence is less clear for passive (secondhand) smoke exposure. We combined individual-level data from 4 population-based studies (the Norway Facial Clefts Study, 1996-2001; the Utah Child and Family Health Study, 1995-2004; the Norwegian Mother and Child Cohort Study, 1999-2009; and the National Birth Defects Prevention Study (United States), 1999-2007) to obtain 4,508 cleft cases and 9,626 controls. We categorized first-trimester passive and active smoke exposure. Multivariable logistic models adjusted for possible confounders (maternal alcohol consumption, use of folic acid supplements, age, body size, education, and employment, plus study fixed effects). Children whose mothers actively smoked had an increased risk of oral clefts (odds ratio (OR) = 1.27, 95% confidence interval (CI): 1.11, 1.46). Children of passively exposed nonsmoking mothers also had an increased risk (OR = 1.14, 95% CI: 1.02, 1.27). Cleft risk was further elevated among babies of smoking mothers who were exposed to passive smoke (OR = 1.51, 95% CI: 1.35, 1.70). Using a large pooled data set, we found a modest association between first-trimester passive smoking and oral clefts that was consistent across populations, diverse study designs, and cleft subtypes. While this association may reflect subtle confounding or bias, we cannot rule out the possibility that passive smoke exposure during pregnancy is teratogenic.

Using the 3D Facial Norms Database to investigate craniofacial sexual dimorphism in healthy children, adolescents, and adults.

BACKGROUND: Although craniofacial sex differences have been extensively studied in humans, relatively little is known about when various dimorphic features manifest during postnatal life. Using cross-sectional data derived from the 3D Facial Norms data repository, we tested for sexual dimorphism of craniofacial soft-tissue morphology at different ages. METHODS: One thousand five hundred fifty-five individuals, pre-screened for craniofacial conditions, between 3 and 25 years of age were placed in to one of six age-defined categories: early childhood, late childhood, puberty, adolescence, young adult, and adult. At each age group, sex differences were tested by ANCOVA for 29 traditional soft-tissue anthropometric measurements collected from 3D facial scans. Additionally, sex differences in shape were tested using a geometric morphometric analysis of 24 3D facial landmarks. RESULTS: Significant (p < 0.05) sex differences were observed in every age group for measurements covering multiple aspects of the craniofacial complex. The magnitude of the dimorphism generally increased with age, with large spikes in the nasal, cranial, and facial measurements observed after puberty. Significant facial shape differences (p < 0.05) were also seen at each age, with some dimorphic features already present in young children (eye fissure inclination) and others emerging only after puberty (mandibular position). CONCLUSIONS: Several craniofacial soft-tissue sex differences were already present in the youngest age group studied, indicating that these differences emerged prior to 3 years of age. The results paint a complex and heterogeneous picture, with different groups of traits exhibiting distinct patterns of dimorphism during ontogeny. The definitive adult male and female facial shape was present following puberty, but arose from numerous distinct changes taking place at earlier stages.

The 3D Facial Norms Database: Part 1. A Web-Based Craniofacial Anthropometric and Image Repository for the Clinical and Research Community.

With the current widespread use of three-dimensional (3D) facial surface imaging in clinical and research environments, there is a growing demand for high-quality craniofacial norms based on 3D imaging technology. The principal goal of the 3D Facial Norms (3DFN) project was to create an interactive, Web-based repository of 3D facial images and measurements. Unlike other repositories, users can gain access to both summary-level statistics and individual-level data, including 3D facial landmark coordinates, 3D-derived anthropometric measurements, 3D facial surface images, and genotypes from every individual in the dataset. The 3DFN database currently consists of 2454 male and female participants ranging in age from 3 to 40 years. The subjects were recruited at four US sites and screened for a history of craniofacial conditions. The goal of this article is to introduce readers to the 3DFN repository by providing a general overview of the project, explaining the rationale behind the creation of the database, and describing the methods used to collect the data. Sex- and age-specific summary statistics (means and standard deviations) and growth curves for every anthropometric measurement in the 3DFN dataset are provided as a supplement available online. These summary statistics and growth curves can aid clinicians in the assessment of craniofacial dysmorphology.