Publications by authors named "Mary L Marazita"

273 Publications

Tools for standardized data collection: Speech, Language, and Hearing measurement protocols in the PhenX Toolkit.

Ann Hum Genet 2021 Sep 28. Epub 2021 Sep 28.

RTI International, Research Triangle Park, North Carolina, USA.

The PhenX Toolkit (https://www.phenxtoolkit.org/) is an online catalog of recommended measurement protocols to facilitate cross-study analyses for biomedical research. An expert review panel (ERP) reviewed and updated the PhenX Toolkit Speech and Hearing domain to improve the precision and consistency of speech, language, and hearing disorder phenotypes. A three-member ERP convened in August 2018 to review the measurement protocols in the PhenX Speech and Hearing domain. Aided by three additional experts in voice assessment, vertigo, and stuttering, the ERP updated the 28 protocols to reflect the latest science and technology. ERP recommendations include six new protocols, five updated protocols (from the same source), and one retired protocol. New additions include two voice-related, three hearing-related, and two speech-related protocols. Additions reflect new phone/tablet applications for hearing and language, and clinical evaluations of voice. "Language" was added to the domain name, which is now "Speech, Language, and Hearing," to represent language-related protocols. These protocols can facilitate the assessment of speech, language, and hearing in clinical and population research. Common data elements (i.e., use of the same variables across studies) used by geneticists, otolaryngologists, audiologists, speech-language pathologists, and in other disciplines can lead to cross-study data integration and increased statistical power when studies are combined.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ahg.12447DOI Listing
September 2021

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

Front Genet 2021 9;12:674642. Epub 2021 Aug 9.

Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, United States.

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 and 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 ( ) mouse line to directly test the function of Prickle1 on the cranial base and observed wider cranial bases in Importantly, we observed that the Prickle1 and Focadhesin proteins co-localize in murine cranial base chondrocytes, and this co-localization is abnormal in the 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fgene.2021.674642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381734PMC
August 2021

Genome scans of facial features in East Africans and cross-population comparisons reveal novel associations.

PLoS Genet 2021 Aug 19;17(8):e1009695. Epub 2021 Aug 19.

Department of Human Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pgen.1009695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375984PMC
August 2021

Genome-Wide Scan for Parent-of-Origin Effects in a sub-Saharan African Cohort With Nonsyndromic Cleft Lip and/or Cleft Palate (CL/P).

Cleft Palate Craniofac J 2021 Aug 12:10556656211036316. Epub 2021 Aug 12.

Department of Oral Pathology, Radiology and Medicine, College of Dentistry, University of Iowa, Iowa, IA, USA.

Objective: Nonsyndromic cleft lip and/or cleft palate (NSCL/P) have multifactorial etiology where genetic factors, gene-environment interactions, stochastic factors, gene-gene interactions, and parent-of-origin effects (POEs) play cardinal roles. POEs arise when the parental origin of alleles differentially impacts the phenotype of the offspring. The aim of this study was to identify POEs that can increase risk for NSCL/P in humans using a genome-wide dataset.

Methods: The samples (174 case-parent trios from Ghana, Ethiopia, and Nigeria) included in this study were from the African only genome wide association studies (GWAS) that was published in 2019. Genotyping of individual DNA using over 2 million multiethnic and African ancestry-specific single-nucleotide polymorphisms from the Illumina Multi-Ethnic Genotyping Array v2 15070954 A2 (genome build GRCh37/hg19) was done at the Center for Inherited Diseases Research. After quality control checks, PLINK was employed to carry out POE analysis employing the pooled subphenotypes of NSCL/P.

Results: We observed possible hints of POEs at a cluster of genes at a 1 mega base pair window at the major histocompatibility complex class 1 locus on chromosome 6, as well as at other loci encompassing candidate genes such as , , , , , , , , , lncRNAs, microRNA, antisense RNAs, , , and .

Conclusion: Findings from our study suggest that some loci may increase the risk for NSCL/P through POEs. Additional studies are required to confirm these suggestive loci in NSCL/P etiology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/10556656211036316DOI Listing
August 2021

Genome-Wide Association Study (GWAS) of dental caries in diverse populations.

BMC Oral Health 2021 07 26;21(1):377. Epub 2021 Jul 26.

Department of Oral and Craniofacial Sciences, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA.

Background: Dental caries is one of the most common chronic diseases and is influenced by a complex interplay of genetic and environmental factors. Most previous genetic studies of caries have focused on identifying genes that contribute to dental caries in specific ethnic groups, usually of European descent.

Methods: The aim of this study is to conduct a genome-wide association study (GWAS) to identify associations affecting susceptibility to caries in a large multiethnic population from Argentina, the Philippines, Guatemala, Hungary, and the USA, originally recruited for studies of orofacial clefts (POFC, N = 3686). Ages of the participants ranged from 2 to 12 years for analysis of the primary dentition, and 18-60 years for analysis of the permanent dentition. For each participant, dental caries was assessed by counts of decayed and filled teeth (dft/DFT) and genetic variants (single nucleotide polymorphisms, SNPs) were genotyped or imputed across the entire genome. Caries was analyzed separately for the primary and permanent dentitions, with age, gender, and presence/absence of any type of OFC treated as covariates. Efficient Mixed-Model Association eXpedited (EMMAX) was used to test genetic association, while simultaneously accounting for relatedness and stratification.

Results: We identified several suggestive loci (5 × 10 < P < 5 × 10) within or near genes with plausible biological roles for dental caries, including a cluster of taste receptor genes (TAS2R38, TAS2R3, TAS2R4, TASR25) on chromosome 7 for the permanent dentition analysis, and DLX3 and DLX4 on chromosome 17 for the primary dentition analysis. Genome-wide significant results were seen with SNPs in the primary dentition only; however, none of the identified genes near these variants have known roles in cariogenesis.

Conclusion: The results of this study warrant further investigation and may lead to a better understanding of cariogenesis in diverse populations, and help to improve dental caries prediction, prevention, and/or treatment in future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12903-021-01670-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8311973PMC
July 2021

Facial Anthropometry Measurements Using Three-Dimensional Stereophotogrammetry Analysis Among Nigerians.

J Craniofac Surg 2021 Jul 23. Epub 2021 Jul 23.

Department of Oral and Maxillofacial Surgery, Lagos University Teaching Hospital, Idi-Araba, Lagos Department of Archeology and Anthropology, University of Ibadan, Ibadan Department of Oral and Maxillofacial Surgery, College of Medicine, University of Lagos, Idi-Araba, Lagos, Nigeria Department of Oral Pathology, Radiology and Medicine, University of Iowa, Iowa City, IA Department of Orthodontics, University of Dundee, Dundee, UK Center for Craniofacial and Dental Genetics, Department of Oral Biology and Human Genetics, University of Pittsburgh, Pittsburgh, PA.

Abstract: This study aimed to determine the normative facial anthropometry measurement among Nigerians using three-dimensional stereophotogrammetry analysis.This study was carried out in Lagos, Nigeria over a period of 3 years. The sample population was Nigerians of diverse ethnic groups, age 16 and above with no history of congenital or acquired craniofacial deformities.A total of 452 subjects participated in the study with 56.2% males and 43.8% females. Most of the participants were between the ages of 25 to 49 (54.4%), 40.7% were less than 25 years of age and only 4.4% were more than 50 years old. The mean body mass index (BMI) for males was 22.7 and 23.4 for females. Mean values of upper facial height, midfacial height, lower facial height, intercanthal distance, interpupillary distance, upper facial width, and lower facial width are 69.13 ± 5.91, 49.89 ± 3.56, 67.85 ± 6.12, 35.19 ± 3.20, 67.04 ± 3.67, 139.43 ± 7.11, and 124.29 ± 9.72 mm, respectively. The upper facial height, commissure width, upper lip length, and lower jaw width were significantly affected by age, while the BMI of an individual was a determinant of the interpupillary distance, facial width, and lower jaw width.This study demonstrated that there was a statistically significant difference in the facial dimensions of males when compared to females across all ages among the study population. The authors also observed that age and BMI are significant predictors of variations in some of the measurements.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SCS.0000000000008036DOI Listing
July 2021

Predictors of use of dental care by children in north-central Appalachia in the USA.

PLoS One 2021 22;16(7):e0250488. Epub 2021 Jul 22.

Center for Oral Health Research in Appalachia, Appalachia, New York, United States of America.

Use of dental services in childhood, especially preventive care, is associated with many important oral health outcomes throughout life. The Andersen behavioral model of healthcare utilization posits that predisposing characteristics, enabling resources, and need factors predict utilization in oral and other healthcare domains. Inequities that produce lower utilization of dental services in north-central Appalachia have been documented in comparison to the USA generally. Additionally, within Appalachia, there are disparities, such as those across different states related to varying public policies and resources supporting healthcare. Predictors of dental utilization in Appalachia have been a focus in adults, but less so in children. The aim of the current study was to understand predictors of dental utilization in children in north-central Appalachia in order to inform future research about how to intervene to address these disparities. In this study, there were 1,178 children, ages 1 through 10 years, from selected representative counties in West Virginia and Pennsylvania, along with a parent/caregiver, who were part of the Center for Oral Health Research in Appalachia (COHRA1) cohort. Use of dental services by their child was indicated by parents/caregivers, who also reported on sociodemographic, dental care-related anxiety and fear, and values and attitudes associated with oral healthcare. Results indicated that use of professional dental services by children was related to child age, dental anxiety and fear, and parental oral health values and attitudes. Older children in this age group, those who evidenced more dental care-related anxiety and fear, and whose parent/caregiver placed higher value on oral health and healthcare for themselves, were more likely to have had a dental visit in the past year.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250488PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8297786PMC
July 2021

Pleiotropy method reveals genetic overlap between orofacial clefts at multiple novel loci from GWAS of multi-ethnic trios.

PLoS Genet 2021 07 9;17(7):e1009584. Epub 2021 Jul 9.

Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America.

Based on epidemiologic and embryologic patterns, nonsyndromic orofacial clefts- the most common craniofacial birth defects in humans- are commonly categorized into cleft lip with or without cleft palate (CL/P) and cleft palate alone (CP), which are traditionally considered to be etiologically distinct. However, some evidence of shared genetic risk in IRF6, GRHL3 and ARHGAP29 regions exists; only FOXE1 has been recognized as significantly associated with both CL/P and CP in genome-wide association studies (GWAS). We used a new statistical approach, PLACO (pleiotropic analysis under composite null), on a combined multi-ethnic GWAS of 2,771 CL/P and 611 CP case-parent trios. At the genome-wide significance threshold of 5 × 10-8, PLACO identified 1 locus in 1q32.2 (IRF6) that appears to increase risk for one OFC subgroup but decrease risk for the other. At a suggestive significance threshold of 10-6, we found 5 more loci with compelling candidate genes having opposite effects on CL/P and CP: 1p36.13 (PAX7), 3q29 (DLG1), 4p13 (LIMCH1), 4q21.1 (SHROOM3) and 17q22 (NOG). Additionally, we replicated the recognized shared locus 9q22.33 (FOXE1), and identified 2 loci in 19p13.12 (RAB8A) and 20q12 (MAFB) that appear to influence risk of both CL/P and CP in the same direction. We found locus-specific effects may vary by racial/ethnic group at these regions of genetic overlap, and failed to find evidence of sex-specific differences. We confirmed shared etiology of the two OFC subtypes comprising CL/P, and additionally found suggestive evidence of differences in their pathogenesis at 2 loci of genetic overlap. Our novel findings include 6 new loci of genetic overlap between CL/P and CP; 3 new loci between pairwise OFC subtypes; and 4 loci not previously implicated in OFCs. Our in-silico validation showed PLACO is robust to subtype-specific effects, and can achieve massive power gains over existing approaches for identifying genetic overlap between disease subtypes. In summary, we found suggestive evidence for new genetic regions and confirmed some recognized OFC genes either exerting shared risk or with opposite effects on risk to OFC subtypes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pgen.1009584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270211PMC
July 2021

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

J Craniofac Surg 2021 Jul 20. Epub 2021 Jul 20.

Department of Oral and Craniofacial Sciences, Center for Craniofacial and Dental Genetics, University of Pittsburgh, Pittsburgh, PA Department of Pediatrics, College of Medicine, Institute of Human Genetics, National Institutes of Health, University of the Philippines Manila, Manila Philippine Genome Center, University of the Philippines System, Quezon, The Philippines Department of Oral Pathology, Radiology and Medicine, University of Iowa, Iowa City, IA Department of Oral and Maxillofacial Surgery, College of Medicine, University of Lagos, Lagos, Nigeria Fundación Clínica Noel, Medellin, Colombia Department of Orthodontics and The Iowa Institute for Oral Health Research, University of Iowa, Iowa City, IA Dental and Craniofacial Genomics Core, School of Dental Medicine, Medical Science Campus, University of Puerto Rico, San Juan, Puerto Rico Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SCS.0000000000007796DOI Listing
July 2021

Associations Between Salivary Bacteriome Diversity and Salivary Human Herpesvirus Detection in Early Childhood: A Prospective Cohort Study.

J Pediatric Infect Dis Soc 2021 Sep;10(8):856-863

Department of Epidemiology, Center for Molecular and Clinical Epidemiology of Infectious Diseases, University of Michigan School of Public Health, Ann Arbor, Michigan, USA.

Background: The bacteriome is associated with susceptibility to some eukaryotic viruses, but no study has examined associations between the salivary bacteriome and human herpesviruses (HHVs). We provide new prevalence and incidence estimates for salivary herpesviruses detection and estimate associations with bacteriome diversity in young children.

Methods: Salivary samples collected at ages ~2, 8, 12, and 24 months from 153 children participating in the Center for Oral Health Research in Appalachia cohort 2 (COHRA2) were screened for HHVs using the Fast-Track Neuro9 multiplex PCR assay, and for the bacteriome using 16S rRNA amplicon sequencing. We used Cox proportional hazard models to test for associations between the salivary bacteriome and hazards of cytomegalovirus (CMV) and human herpesvirus-6 (HHV6).

Results: CMV, HHV6, and Epstein-Barr virus (EBV) were detected at all visits. Human herpesvirus-7 (HHV7) was first detected at the 8-month visit and herpes simplex virus 1 (HSV1) was only detected at the 12-month visit. Varicella-zoster virus, herpes simplex virus 2, and human herpesvirus-8 were never detected. HHV6 (24-month cumulative incidence: 73.8%) and CMV (24-month cumulative incidence: 32.3%) were detected most frequently. Increasing salivary bacteriome diversity was associated with longer survival to first detection of CMV (hazard ratio [95% CI]: 0.24 [0.12, 0.49]) and HHV6 (hazard ratio [95% CI]: 0.24 [0.13, 0.44]).

Conclusion: CMV, HHV6, EBV, HHV7, and HSV1 were detected in the saliva during the first 2 years of life. Time to first detection of CMV and HHV6 was associated with salivary bacteriome diversity, suggesting a possible interaction between HHVs and the salivary bacteriome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jpids/piab044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8459089PMC
September 2021

FAT4 identified as a potential modifier of orofacial cleft laterality.

Genet Epidemiol 2021 10 15;45(7):721-735. Epub 2021 Jun 15.

Department of Human Genetics, Emory University, Atlanta, Georgia, USA.

Orofacial clefts (OFCs) are common (1 in 700 births) congenital malformations that include a cleft lip (CL) and cleft lip and palate (CLP). These OFC subtypes are also heterogeneous themselves, with the CL occurring on the left, right, or both sides of the upper lip. Unilateral CL and CLP have a 2:1 bias towards left-sided clefts, suggesting a nonrandom process. Here, we performed a study of left- and right-sided clefts within the CL and CLP subtypes to better understand the genetic factors controlling cleft laterality. We conducted genome-wide modifier analyses by comparing cases that had right unilateral CL (RCL; N = 130), left unilateral CL (LCL; N = 216), right unilateral CLP (RCLP; N = 416), or left unilateral CLP (LCLP; N = 638), and identified a candidate region on 4q28, 400 kb downstream from FAT4, that approached genome-wide significance for LCL versus RCL (p = 8.4 × 10 ). Consistent with its potential involvement as a genetic modifier of CL, we found that Fat4 exhibits a specific domain of expression in the mesenchyme of the medial nasal processes that form the median upper lip. Overall, these results suggest that the epidemiological similarities in left- to right-sided clefts in CL and CLP are not reflected in the genetic association results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/gepi.22420DOI Listing
October 2021

Variant analyses of candidate genes in orofacial clefts in multi-ethnic populations.

Oral Dis 2021 Jun 1. Epub 2021 Jun 1.

Department of Oral Pathology, Radiology and Medicine, College of Dentistry, University of Iowa, Iowa City, IA, USA.

Objectives: Cleft lip with/without cleft palate and cleft palate only is congenital birth defects where the upper lip and/or palate fail to fuse properly during embryonic facial development. Affecting ~1.2/1000 live births worldwide, these orofacial clefts impose significant social and financial burdens on affected individuals and their families. Orofacial clefts have a complex etiology resulting from genetic variants combined with environmental covariates. Recent genome-wide association studies and whole-exome sequencing for orofacial clefts identified significant genetic associations and variants in several genes. Of these, we investigated the role of common/rare variants in SHH, RORA, MRPL53, ACVR1, and GDF11.

Materials And Methods: We sequenced these five genes in 1255 multi-ethnic cleft lip with/without palate and cleft palate only samples in order to find variants that may provide potential explanations for the missing heritability of orofacial clefts. Rare and novel variants were further analyzed using in silico predictive tools.

Results: Ninteen total variants of interest were found, with variant types including stop-gain, missense, synonymous, intronic, and splice-site variants. Of these, 3 novel missense variants were found, one in SHH, one in RORA, and one in GDF11.

Conclusion: This study provides evidence that variants in SHH, RORA, MRPL53, ACVR1, and GDF11 may contribute to risk of orofacial clefts in various populations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/odi.13932DOI Listing
June 2021

Using the PhenX Toolkit to Select Standard Measurement Protocols for Your Research Study.

Curr Protoc 2021 May;1(5):e149

RTI International, Research Triangle Park, North Carolina.

The goals of PhenX (consensus measures for Phenotypes and eXposures) are to promote the use of standard measurement protocols and to help investigators identify opportunities for collaborative research and cross-study analysis, thus increasing the impact of individual studies. The PhenX Toolkit (https://www.phenxtoolkit.org/) offers high-quality, well-established measurement protocols to assess phenotypes and exposures in studies with human participants. The Toolkit contains protocols representing 29 research domains and 6 specialty collections of protocols that add depth to the Toolkit in specific research areas (e.g., COVID-19, Social Determinants of Health [SDoH], Blood Sciences Research [BSR], Mental Health Research [MHR], Tobacco Regulatory Research [TRR], and Substance Abuse and Addiction [SAA]). Protocols are recommended for inclusion in the PhenX Toolkit by Working Groups of domain experts using a consensus process that includes input from the scientific community. For each PhenX protocol, the Toolkit provides a detailed description, the rationale for inclusion, and supporting documentation. Users can browse protocols in the Toolkit, search the Toolkit using keywords, or use Browse Protocols Tree to identify protocols of interest. The PhenX Toolkit provides data dictionaries compatible with the database of Genotypes and Phenotypes (dbGaP), Research Electronic Data Capture (REDCap) data submission compatibility, and data collection worksheets to help investigators incorporate PhenX protocols into their study design. The PhenX Toolkit provides resources to help users identify published studies that used PhenX protocols. © 2021 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol: Using the PhenX Toolkit to support or extend study design.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cpz1.149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251725PMC
May 2021

Detecting Gene-Environment Interaction for Maternal Exposures Using Case-Parent Trios Ascertained Through a Case With Non-Syndromic Orofacial Cleft.

Front Cell Dev Biol 2021 16;9:621018. Epub 2021 Apr 16.

Department of Epidemiology, School of Public Health, Johns Hopkins University, Baltimore, MD, United States.

Two large studies of case-parent trios ascertained through a proband with a non-syndromic orofacial cleft (OFC, which includes cleft lip and palate, cleft lip alone, or cleft palate alone) were used to test for possible gene-environment (G × E) interaction between genome-wide markers (both observed and imputed) and self-reported maternal exposure to smoking, alcohol consumption, and multivitamin supplementation during pregnancy. The parent studies were as follows: GENEVA, which included 1,939 case-parent trios recruited largely through treatment centers in Europe, the United States, and Asia, and 1,443 case-parent trios from the Pittsburgh Orofacial Cleft Study (POFC) also ascertained through a proband with an OFC including three major racial/ethnic groups (European, Asian, and Latin American). Exposure rates to these environmental risk factors (maternal smoking, alcohol consumption, and multivitamin supplementation) varied across studies and among racial/ethnic groups, creating substantial differences in power to detect G × E interaction, but the trio design should minimize spurious results due to population stratification. The GENEVA and POFC studies were analyzed separately, and a meta-analysis was conducted across both studies to test for G × E interaction using the 2 df test of gene and G × E interaction and the 1 df test for G × E interaction alone. The 2 df test confirmed effects for several recognized risk genes, suggesting modest G × E effects. This analysis did reveal suggestive evidence for G × Vitamin interaction for on 1p36 located about 3 Mb from , a recognized risk gene. Several regions gave suggestive evidence of G × E interaction in the 1 df test. For example, for G × Smoking interaction, the 1 df test suggested markers in on 9q31.3 from meta-analysis. Markers near also showed suggestive evidence in the 1 df test for G × Alcohol interaction, and rs41117 near (a.k.a. ) also gave suggestive significance in the meta-analysis of the 1 df test for G × Vitamin interaction. While it remains quite difficult to obtain definitive evidence for G × E interaction in genome-wide studies, perhaps due to small effect sizes of individual genes combined with low exposure rates, this analysis of two large case-parent trio studies argues for considering possible G × E interaction in any comprehensive study of complex and heterogeneous disorders such as OFC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcell.2021.621018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085423PMC
April 2021

Genome-Wide Association Study of Non-syndromic Orofacial Clefts in a Multiethnic Sample of Families and Controls Identifies Novel Regions.

Front Cell Dev Biol 2021 9;9:621482. Epub 2021 Apr 9.

Center for Craniofacial and Dental Genetics, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, United States.

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 vary in prevalence by ethnicity. Africans have the lowest prevalence of OFCs (~ 1/2,500), Asians have the highest prevalence (~1/500), Europeans and Latin Americans lie somewhere in the middle (~1/800 and 1/900, respectively). Thus, ethnicity appears to be a major determinant of the risk of developing OFC. The Pittsburgh Orofacial Clefts Multiethnic study was designed to explore this ethnic variance, comprising a large number of families and individuals (~12,000 individuals) from multiple populations worldwide: US and Europe, Asians, mixed Native American/Caucasians, and Africans. In this current study, we analyzed 2,915 OFC cases, 6,044 unaffected individuals related to the OFC cases, and 2,685 controls with no personal or family history of OFC. Participants were grouped by their ancestry into African, Asian, European, and Central and South American subsets, and genome-wide association run on the combined sample as well as the four ancestry-based groups. We observed 22 associations to cleft lip with or without cleft palate at 18 distinct loci with -values < 1e-06, including 10 with genome-wide significance (<5e-08), in the combined sample and within ancestry groups. Three loci - 2p12 (rs62164740, = 6.27e-07), 10q22.2 (rs150952246, = 3.14e-07), and 10q24.32 (rs118107597, = 8.21e-07) are novel. Nine were in or near known OFC loci - , 8q24.21, , and . The majority of the associations were observed only in the combined sample, European, and Central and South American groups. We investigated whether the observed differences in association strength were (a) purely due to sample sizes, (b) due to systematic allele frequency difference at the population level, or (c) due to the fact certain OFC-causing variants confer different amounts of risk depending on ancestral origin, by comparing effect sizes to observed allele frequencies of the effect allele in our ancestry-based groups. While some of the associations differ due to systematic differences in allele frequencies between groups, others show variation in effect size despite similar frequencies across ancestry groups.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcell.2021.621482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062975PMC
April 2021

The PAX1 locus at 20p11 is a potential genetic modifier for bilateral cleft lip.

HGG Adv 2021 Apr;2(2)

) Department of Human Genetics, Emory University, Atlanta, GA, 30322, USA.

Nonsyndromic orofacial clefts (OFCs) are a common birth defect and are phenotypically heterogenous in the structure affected by the cleft - cleft lip (CL) and cleft lip and palate (CLP) - as well as other features, such as the severity of the cleft. Here, we focus on bilateral and unilateral clefts as one dimension of OFC severity, because the genetic architecture of these subtypes is not well understood. We tested for subtype-specific genetic associations in 44 bilateral CL (BCL) cases, 434 unilateral CL (UCL) cases, 530 bilateral CLP cases (BCLP), 1123 unilateral CLP (UCLP) cases, and unrelated controls (N = 1626), using a mixed-model approach. While no novel loci were found, the genetic architecture of UCL was distinct compared to BCL, with 44.03% of suggestive loci having different effects between the two subtypes. To further understand the subtype-specific genetic risk factors, we performed a genome-wide scan for modifiers and found a significant modifier locus on 20p11 (p=7.53×10), 300kb downstream of , that associated with higher odds of BCL vs. UCL, and replicated in an independent cohort (p=0.0018) with no effect in BCLP (p>0.05). We further found that this locus was associated with normal human nasal shape. Taken together, these results suggest bilateral and unilateral clefts may have different genetic architectures. Moreover, our results suggest BCL, the rarest form of OFC, may be genetically distinct from the other OFC subtypes. This expands our understanding of modifiers for OFC subtypes and further elucidates the genetic mechanisms behind the phenotypic heterogeneity in OFCs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.xhgg.2021.100025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018676PMC
April 2021

The Intersection of the Genetic Architectures of Orofacial Clefts and Normal Facial Variation.

Front Genet 2021 22;12:626403. Epub 2021 Feb 22.

Department of Electrical Engineering, ESAT/PSI, KU Leuven, Leuven, Belgium.

Unaffected relatives of individuals with non-syndromic cleft lip with or without cleft palate (NSCL/P) show distinctive facial features. The presence of this facial endophenotype is potentially an expression of underlying genetic susceptibility to NSCL/P in the larger unselected population. To explore this hypothesis, we first partitioned the face into 63 partially overlapping regions representing global-to-local facial morphology and then defined endophenotypic traits by contrasting the 3D facial images from 264 unaffected parents of individuals with NSCL/P versus 3,171 controls. We observed distinct facial features between parents and controls across 59 global-to-local facial segments at nominal significance ( ≤ 0.05) and 52 segments at Bonferroni corrected significance ( < 1.2 × 10), respectively. Next, we quantified these distinct facial features as univariate traits in another dataset of 8,246 unaffected European individuals and performed a genome-wide association study. We identified 29 independent genetic loci that were associated ( < 5 × 10) with at least one of the tested endophenotypic traits, and nine genetic loci also passed the study-wide threshold ( < 8.47 × 10). Of the 29 loci, 22 were in proximity of loci previously associated with normal facial variation, 18 were near genes that show strong evidence in orofacial clefting (OFC), and another 10 showed some evidence in OFC. Additionally, polygenic risk scores for NSCL/P showed associations with the endophenotypic traits. This study thus supports the hypothesis of a shared genetic architecture of normal facial development and OFC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fgene.2021.626403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937973PMC
February 2021

Fluctuating Asymmetry and Sexual Dimorphism in Human Facial Morphology: A Multi-Variate Study.

Symmetry (Basel) 2021 Feb 10;13(2). Epub 2021 Feb 10.

Evolutionary Ecology Group, Department of Biology, University of Antwerp, 2610 Antwerp, Belgium.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/sym13020304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7929517PMC
February 2021

Effects of Male Facial Masculinity on Perceived Attractiveness.

Adapt Human Behav Physiol 2021 Mar 12;7(1):73-88. Epub 2020 Nov 12.

Evolutionary Ecology Group, Department of Biology, University of Antwerp, Antwerp, Belgium.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40750-020-00156-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872150PMC
March 2021

A Multivariate Approach to Determine the Dimensionality of Human Facial Asymmetry.

Symmetry (Basel) 2020 Mar 1;12(3). Epub 2020 Mar 1.

Evolutionary Ecology Group, Department of Biology, University of Antwerp, 2610 Antwerp, Belgium; stefan.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/sym12030348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872143PMC
March 2020

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

Sci Rep 2021 01 12;11(1):748. Epub 2021 Jan 12.

Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-80661-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804299PMC
January 2021

Oral health and related risk indicators in north-central Appalachia differ by rurality.

Community Dent Oral Epidemiol 2021 10 28;49(5):427-436. Epub 2020 Dec 28.

Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.

Objectives: This cross-sectional study assessed differences in oral health and related behaviours and risk indicators by rurality in a north-central Appalachian population using the Andersen behavioural model as a conceptual framework.

Methods: Participants were residents aged 18-59 years (n = 1311) from the Center for Oral Health Research in Appalachia, selected according to a household-based sampling strategy. Rural-Urban Continuum codes (RUC) corresponding to the participants' residences were used to classify participants as rural or urban. Mixed models were used to test rural-urban differences in measures of oral health, related behaviours, and need, enabling, and predisposing risk indicators. Models were adjusted for sociodemographic variables: age, sex, race, income, perceived socioeconomic status, educational attainment and dental insurance.

Results: Rural residents had poorer oral health overall, with fewer sound teeth (β = -1.79), more dental caries (β = 0.27) and higher rates of edentulism (5.2% vs 2.8%). Differences also were observed for dental care utilization and perceived barriers to care. Rural residents were less likely to attend dental visits as often as needed (26.9% vs 42.8%) and were more prone to seek care only after experiencing a dental problem (64.3% vs 43.9%). Rural residents also were more likely to report high costs (89% vs 62.6%) as a major reason for not having dental visits. Rural-urban differences for some oral health characteristics and behaviours could be explained by sociodemographic characteristics, whereas others could not.

Conclusions: This study revealed rural-urban differences in risk indicators and oral health outcomes in north-central Appalachia. Many of these differences were explained, completely or partly, by sociodemographic factors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cdoe.12618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381283PMC
October 2021

Insights into the genetic architecture of the human face.

Nat Genet 2021 01 7;53(1):45-53. Epub 2020 Dec 7.

Department of Electrical Engineering, ESAT/PSI, KU Leuven, Leuven, Belgium.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41588-020-00741-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796995PMC
January 2021

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

Homo 2020 Nov;71(4):273-280

Center for Craniofacial and Dental Genetics, Department of Oral Biology, University of Pittsburgh, Pittsburgh, PA, USA.

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. 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. 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. 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1127/homo/2020/1316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674192PMC
November 2020

Expanding the genetic architecture of nicotine dependence and its shared genetics with multiple traits.

Nat Commun 2020 11 3;11(1):5562. Epub 2020 Nov 3.

Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, 68159, Mannheim, Germany.

Cigarette smoking is the leading cause of preventable morbidity and mortality. Genetic variation contributes to initiation, regular smoking, nicotine dependence, and cessation. We present a Fagerström Test for Nicotine Dependence (FTND)-based genome-wide association study in 58,000 European or African ancestry smokers. We observe five genome-wide significant loci, including previously unreported loci MAGI2/GNAI1 (rs2714700) and TENM2 (rs1862416), and extend loci reported for other smoking traits to nicotine dependence. Using the heaviness of smoking index from UK Biobank (N = 33,791), rs2714700 is consistently associated; rs1862416 is not associated, likely reflecting nicotine dependence features not captured by the heaviness of smoking index. Both variants influence nearby gene expression (rs2714700/MAGI2-AS3 in hippocampus; rs1862416/TENM2 in lung), and expression of genes spanning nicotine dependence-associated variants is enriched in cerebellum. Nicotine dependence (SNP-based heritability = 8.6%) is genetically correlated with 18 other smoking traits (r = 0.40-1.09) and co-morbidities. Our results highlight nicotine dependence-specific loci, emphasizing the FTND as a composite phenotype that expands genetic knowledge of smoking.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-020-19265-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642344PMC
November 2020

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

Cleft Palate Craniofac J 2021 07 28;58(7):847-853. Epub 2020 Oct 28.

Center for Craniofacial and Dental Genetics, Department of Oral Biology, 212605University of Pittsburgh, Pittsburgh, PA, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1055665620967235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079510PMC
July 2021

FaceBase 3: analytical tools and FAIR resources for craniofacial and dental research.

Development 2020 09 21;147(18). Epub 2020 Sep 21.

Human Medical Genetics and Genomics Program, School of Medicine, University of Colorado, Aurora, CO 80045, USA.

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 available to the research community on the FaceBase Hub website. The Hub has developed numerous visualization and analysis tools designed to promote integration of multidisciplinary data while remaining dedicated to the FAIR principles of data management (findability, accessibility, interoperability and reusability) and providing a faceted search infrastructure for locating desired data efficiently. Summaries of the datasets generated by the FaceBase projects from 2014 to 2019 are provided here. FaceBase 3 now welcomes contributions of data on craniofacial and dental development in humans, model organisms and cell lines. Collectively, the FaceBase Consortium, along with other NIH-supported data resources, provide a continuously growing, dynamic and current resource for the scientific community while improving data reproducibility and fulfilling data sharing requirements.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1242/dev.191213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522026PMC
September 2020

Low levels of salivary metals, oral microbiome composition and dental decay.

Sci Rep 2020 09 4;10(1):14640. Epub 2020 Sep 4.

Center for Molecular and Clinical Epidemiology of Infectious Diseases, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI, 48109-2029, USA.

Salivary microbiome composition can change following exposure to environmental toxicants, e.g., heavy metals. We hypothesized that levels of salivary nutrients and metals would correlate with salivary microbiome composition and be associated with dental decay. Here we assess the salivary concentrations of 5 essential minerals (cobalt, copper, manganese, molybdenum, and zinc), 4 metals with some evidence of normal physiological function (chromium, nickel, tungsten, and vanadium), and 12 with known toxicity (antimony, arsenic, barium, beryllium, cadmium, cesium, lead, mercury, platinum, thallium, tin, and uranium), and their associations with salivary microbiome composition and dental decay in 61 children and adults. 16 metals were detected in 54% of participants; 8 were found in all. Marked differences in salivary bacterial taxa were associated with levels of antimony, arsenic, and mercury, after adjusting for multiple testing. Further, antimony levels were associated with the presence of decayed teeth. Thus, salivary metal levels, even at low concentrations, may impact oral health.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-71495-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7474081PMC
September 2020

Genome-wide Enrichment of De Novo Coding Mutations in Orofacial Cleft Trios.

Am J Hum Genet 2020 07 22;107(1):124-136. Epub 2020 Jun 22.

Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address:

Although de novo mutations (DNMs) are known to increase an individual's risk of congenital defects, DNMs have not been fully explored regarding orofacial clefts (OFCs), one of the most common human birth defects. Therefore, whole-genome sequencing of 756 child-parent trios of European, Colombian, and Taiwanese ancestry was performed to determine the contributions of coding DNMs to an individual's OFC risk. Overall, we identified a significant excess of loss-of-function DNMs in genes highly expressed in craniofacial tissues, as well as genes associated with known autosomal dominant OFC syndromes. This analysis also revealed roles for zinc-finger homeobox domain and SOX2-interacting genes in OFC etiology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajhg.2020.05.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332647PMC
July 2020
-->