Richard Spritz

Richard Spritz
University of Colorado | UCD

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422
Publications
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Introduction
Skills and Expertise

Publications

Publications (422)
Article
Background In clinical genetics, establishing an accurate nosology requires analysis of variations in both aetiology and the resulting phenotypes. At the phenotypic level, recognising typical facial gestalts has long supported clinical and molecular diagnosis; however, the objective analysis of facial phenotypic variation remains underdeveloped. In...
Preprint
Transcriptional regulation displays extensive robustness, but human genetics indicate sensitivity to transcription factor (TF) dosage. Reconciling such observations requires quantitative studies of TF dosage effects at trait-relevant ranges, which are lacking to date. TFs play central roles in both normal-range and disease-associated variation in f...
Article
One of the primary difficulties in treating patients with genetic syndromes is diagnosing their condition. Many syndromes are associated with characteristic facial features that can be imaged and utilized by computer-assisted diagnosis systems. In this work, we develop a novel 3D facial surface modeling approach with the objective of maximizing dia...
Chapter
Vitiligo is an autoimmune disease that results in destruction of skin melanocytes and patches of white skin and hair. Family studies of vitiligo demonstrated that a strong, but complex genetic component underlies disease risk and that vitiligo often occurs with other autoimmune diseases, suggesting shared autoimmune susceptibility. Genome‐wide link...
Article
Full-text available
Identification and delineation of craniofacial characteristics support the clinical and molecular diagnosis of genetic syndromes. Deep learning (DL) frameworks for syndrome identification from 2D facial images are trained on large clinical datasets using standard convolutional neural networks for classification. In contrast, despite the increased a...
Article
Full-text available
Similarity in facial characteristics between relatives suggests a strong genetic component underlies facial variation. While there have been numerous studies of the genetics of facial abnormalities and, more recently, single nucleotide polymorphism (SNP) genome-wide association studies (GWAS) of normal facial variation, little is known about the ro...
Article
Full-text available
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 fo...
Article
Full-text available
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 norm...
Article
Full-text available
Background Copy number variations (CNVs) account for a substantial proportion of inter-individual genomic variation. However, a majority of genomic variation studies have focused on single-nucleotide variations (SNVs), with limited genome-wide analysis of CNVs in large cohorts, especially in populations that are under-represented in genetic studies...
Preprint
Full-text available
Background Copy number variations (CNVs) account for a substantial proportion of inter-individual genomic variation. However, a majority of genomic variation studies have focused on single-nucleotide variations (SNVs), with limited genome-wide analysis of CNVs in large cohorts, especially in populations that are under-represented in genetic studies...
Article
Full-text available
The reduction of food intake during pregnancy is part of many cultural and religious traditions around the world. The impact of such practices on fetal growth and development are poorly understood. Here, we examined the patterns of diet intake among Maasai pregnant women and assessed their effect on newborn morphometrics. We recruited 141 mother-in...
Article
The FaceBase Consortium was established by the National Institute of Dental and Craniofacial Research in 2009 as a 'big data' resource for the craniofacial research community. Over the past decade, researchers have deposited hundreds of annotated and curated datasets on both normal and disordered craniofacial development in FaceBase, all freely ava...
Article
Vitiligo is a complex disease in which autoimmune destruction of epidermal melanocytes results in patches of depigmented white skin. Vitiligo has an estimated prevalence of about 0.2–2% in different populations and approximately 0.4% in the European-derived white (EUR) population. The fraction of disease risk attributable to genetic variation, term...
Article
Full-text available
3D facial landmarks are known to be diagnostically relevant biometrics for many genetic syndromes. The objective of this study was to extend a state-of-the-art image-based 2D facial landmarking algorithm for the challenging task of 3D landmark identification on subjects with genetic syndromes, who often have moderate to severe facial dysmorphia. Th...
Article
Full-text available
Deep phenotyping is an emerging trend in precision medicine for genetic disease. The shape of the face is affected in 30–40% of known genetic syndromes. Here, we determine whether syndromes can be diagnosed from 3D images of human faces. We analyzed variation in three-dimensional (3D) facial images of 7057 subjects: 3327 with 396 different syndrome...
Article
Autoimmune vitiligo is a complex disease involving polygenic risk from at least 50 loci previously identified by GWAS. The objectives of this study were to estimate and compare vitiligo heritability in European-derived patients using both family-based and "deep imputation" genotype-based approaches. We estimated family-based heritability (h2FAM) by...
Article
Vitiligo is an autoimmune disease in which destruction of skin melanocytes results in patches of white skin and hair. Genome‐wide linkage studies and GWAS in European ancestry cases identified over 50 vitiligo susceptibility loci, defining a model of melanocyte‐directed autoimmunity. Vitiligo heritability is exceedingly high, ~2/3 coming from commo...
Chapter
Large-scale epidemiological surveys have shown that most cases of vitiligo occur sporadically, though about 15–20% of patients report one or more affected relatives. The rationale for genetic studies of vitiligo susceptibility is that underlying genes are involved in mediating disease causation, either increasing or decreasing risk (protective). Th...
Article
Full-text available
Vitiligo is an autoimmune disease that results in patches of depigmented skin and hair. Previous genome-wide association studies(GWASs) of vitiligo have identified 50 susceptibility loci. Variants at the associated loci are generally common and have individually small effects on risk. Most vitiligo cases are ‘‘simplex,’’ where there is no family hi...
Article
Full-text available
Many immune diseases occur at different rates among people with schizophrenia compared to the general population. Here, we evaluated whether this phenomenon might be explained by shared genetic risk factors. We used data from large genome-wide association studies to compare the genetic architecture of schizophrenia to 19 immune diseases. First, we...
Preprint
Full-text available
Epidemiological studies indicate that many immune diseases occur at different rates among people with schizophrenia compared to the general population. Here, we evaluated whether this phenotypic correlation between immune diseases and schizophrenia might be explained by shared genetic risk factors ( genetic correlation ). We used data from a large...
Article
Full-text available
Vitiligo is an autoimmune disease in which melanocyte destruction causes skin depigmentation, with 49 loci known from previous GWAS. Aiming to define vitiligo subtypes, we discovered that age-of-onset is bimodal; one-third of cases have early onset (mean 10.3 years) and two-thirds later onset (mean 34.0 years). In the early-onset subgroup we found...
Article
Full-text available
The International Federation of Pigment Cell Societies (IFPCS) held its XXIII triennial International Pigment Cell Conference (IPCC) in Denver, Colorado in August 2017. The goal of the summit was to provide a venue promoting a vibrant interchange among leading basic and clinical researchers working on leading-edge aspects of melanocyte biology and...
Chapter
Vitiligo is an autoimmune disease that results in destruction of skin melanocytes and patches of white skin and hair. Family studies of vitiligo demonstrated that a strong, but complex genetic component underlies disease risk and that vitiligo often occurs with other autoimmune diseases, suggesting shared autoimmune susceptibility. Genome‐wide link...
Article
In this perspective, we identify emerging frontiers in clinical and basic research of melanocyte biology and its associated biomedical disciplines. We describe challenges and opportunities in clinical and basic research of normal and diseased melanocytes that impact current approaches to research in melanoma and the dermatological sciences. We focu...
Preprint
Full-text available
The International Federation of Pigment Cell Societies (IFPCS) held its XXIII triennial International Pigment Cell Conference (IPCC) in Denver, Colorado in August 2017. The goal of the summit was to provide a venue promoting a vibrant interchange among leading basic and clinical researchers working on leading-edge aspects of melanocyte biology and...
Article
Full-text available
Background: Genodermatoses represent genetic anomalies of skin tissues including hair follicles, sebaceous glands, eccrine glands, nails, and teeth. Ten consanguineous families segregating various genodermatosis phenotypes were investigated in the present study. Methods: Homozygosity mapping, exome, and Sanger sequencing were employed to search...
Article
Full-text available
Objectives: Morphological integration, or the tendency for covariation, is commonly seen in complex traits such as the human face. The effects of growth on shape, or allometry, represent a ubiquitous but poorly understood axis of integration. We address the question of to what extent age and measures of size converge on a single pattern of allomet...
Article
Variation in the shape of the human face and in stature is determined by complex interactions between genetic and environmental influences. One such environmental influence is malnourishment, which can result in growth faltering, usually diagnosed by means of comparing an individual's stature with a set of age-appropriate standards. These standards...
Chapter
Full-text available
Human facial morphology broadly encompasses several distinct facial structures that alone and together contain enormous variations which contribute to our physical identities as both individuals and members of families and populations. The human face comprises an assemblage of multifactorial complex traits, with clear genetic components and known e...
Article
Full-text available
Vitiligo reflects simultaneous contributions of multiple genetic risk factors and environmental triggers. Genomewide association studies have discovered approximately 50 genetic loci contributing to vitiligo risk. At many vitiligo susceptibility loci, the relevant genes and DNA sequence variants are identified. Many encode proteins involved in immu...
Article
The rapid increase in gene-centric biological knowledge coupled with analytic approaches for genomewide data integration provides an opportunity to develop systems-level understanding of facial development. Experimental analyses have demonstrated the importance of signaling between the surface ectoderm and the underlying mesenchyme in coordinating...
Article
Inflammasomes are mediators of inflammation, and constitutively activated NLRP3 inflammasomes have been linked to interleukin-1β (IL-1β)-mediated tumorigenesis in human melanoma. Whereas NLRP3 regulation of caspase-1 activation requires the adaptor protein ASC (apoptosis-associated speck-like protein containing a CARD (caspase recruitment domain)),...
Article
Full-text available
The human face is an array of variable physical features that together make each of us unique and distinguishable. Striking familial facial similarities underscore a genetic component, but little is known of the genes that underlie facial shape differences. Numerous studies have estimated facial shape heritability using various methods. Here, we us...
Article
Development translates genetic variation into a multivariate pattern of phenotypic variation, distributing it among traits in a nonuniform manner. As developmental processes are largely shared within species, this suggests that heritable phenotypic variation will be patterned similarly, in spite of the different segregating alleles. To investigate...
Article
Automated phenotyping is essential for the creation of large, highly standardized datasets from anatomical imaging data. Such datasets can support large-scale studies of complex traits or clinical studies related to precision medicine or clinical trials. We have developed a method that generates three-dimensional landmark data that meet the require...
Article
Background: Progressive symmetric erythrokeratoderma (PSEK) is a rare skin disorder characterised by symmetrically distributed demarcated hyperkeratotic plaques, often with associated palmoplantar hyperkeratosis, with new plaques appearing over time. Most cases are inherited in an autosomal dominant manner, although a few cases exhibit apparent au...
Poster
The face is one of the most distinguishing characteristics of the human body, and similarity between relatives points towards a strong genetic component in normal facial development. However, little is known about the genetic factors underlying normal facial appearance, particularly Copy Number Variations (CNVs). CNVs are a substantial source of no...
Article
Vitiligo is an autoimmune disease in which depigmented skin results from the destruction of melanocytes, with epidemiological association with other autoimmune diseases. In previous linkage and genome-wide association studies (GWAS1 and GWAS2), we identified 27 vitiligo susceptibility loci in patients of European ancestry. We carried out a third GW...
Article
Full-text available
Isolated congenital nail clubbing (ICNC; OMIM 119900) is a rare genodermatosis in which bilateral, symmetric enlargement of the nail plate and terminal segments of fingers and/or toes results from excessive proliferation of connective tissue between the nail matrix and distal phalanx. Loss of the normal angle between the nail and posterior nail fol...
Article
Full-text available
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...
Article
Full-text available
The human face is a complex assemblage of highly variable yet clearly heritable anatomic structures that together make each of us unique, distinguishable, and recognizable. Relatively little is known about the genetic underpinnings of normal human facial variation. To address this, we carried out a large genomewide association study and two indepen...
Data
Number of SNPs omitted and retained for each quality filter. (DOCX)
Data
Final number of SNPs used in our analysis. (DOCX)
Data
Manhattan plots for lower facial depth. (A) meta-analysis results, (B) Pittsburgh sample results, and (C) Denver sample results. Lines for p-value thresholds set at 5 x 10−8 for genome-wide significance and 5 x 10−7 for suggestive significance. (PDF)
Data
Manhattan plots for nasal protrusion. (A) meta-analysis results, (B) Pittsburgh sample results, and (C) Denver sample results. Lines for p-value thresholds set at 5 x 10−8 for genome-wide significance and 5 x 10−7 for suggestive significance. (PDF)
Data
Manhattan plots for nasal height. (A) meta-analysis results, (B) Pittsburgh sample results, and (C) Denver sample results. Lines for p-value thresholds set at 5 x 10−8 for genome-wide significance and 5 x 10−7 for suggestive significance. (PDF)
Data
Manhattan plots for nasal bridge length. (A) meta-analysis results, (B) Pittsburgh sample results, and (C) Denver sample results. Lines for p-value thresholds set at 5 x 10−8 for genome-wide significance and 5 x 10−7 for suggestive significance. (PDF)
Data
Manhattan plots for labial fissure width. (A) meta-analysis results, (B) Pittsburgh sample results, and (C) Denver sample results. Lines for p-value thresholds set at 5 x 10−8 for genome-wide significance and 5 x 10−7 for suggestive significance. (PDF)
Data
Associations with p-values < 5 x 10−7 for all 20 traits from genome-wide analysis of the Pittsburgh sample. (XLSX)
Data
Associations with p-values < 5 x 10−7 for all 20 traits from genome-wide analysis of the Denver sample. (XLSX)
Data
List of linear distance measurements. (DOCX)