Heritability maps of human face morphology through large-scale automated three-dimensional phenotyping

The human face is a complex trait under strong genetic control, as evidenced by the striking visual similarity between twins. Nevertheless, heritability estimates of facial traits have often been surprisingly low or difficult to replicate. Furthermore, the construction of facial phenotypes that correspond to naturally perceived facial features remains largely a mystery. We present here a large-scale heritability study of face geometry that aims to address these issues. High-resolution, three-dimensional facial models have been acquired on a cohort of 952 twins recruited from the TwinsUK registry, and processed through a novel landmarking workflow, GESSA (Geodesic Ensemble Surface Sampling Algorithm). The algorithm places thousands of landmarks throughout the facial surface and automatically establishes point-wise correspondence across faces. These landmarks enabled us to intuitively characterize facial geometry at a fine level of detail through curvature measurements, yielding accurate heritability maps of the human face (www.heritabilitymaps.info)

Genetic and Dietary Factors Influencing the Progression of Nuclear Cataract.

PURPOSE: To determine the heritability of nuclear cataract progression and to explore prospectively the effect of dietary micronutrients on the progression of nuclear cataract. DESIGN: Prospective cohort study. PARTICIPANTS: Cross-sectional nuclear cataract and dietary measurements were available for 2054 white female twins from the TwinsUK cohort. Follow-up cataract measurements were available for 324 of the twins (151 monozygotic and 173 dizygotic twins). METHODS: Nuclear cataract was measured using a quantitative measure of nuclear density obtained from digital Scheimpflug images. Dietary data were available from EPIC food frequency questionnaires. Heritability was modeled using maximum likelihood structural equation twin modeling. Association between nuclear cataract change and micronutrients was investigated using linear and multinomial regression analysis. The mean interval between baseline and follow-up examination was 9.4 years. MAIN OUTCOME MEASURES: Nuclear cataract progression. RESULTS: The best-fitting model estimated that the heritability of nuclear cataract progression was 35% (95% confidence interval [CI], 13-54), and individual environmental factors explained the remaining 65% (95% CI, 46-87) of variance. Dietary vitamin C was protective against both nuclear cataract at baseline and nuclear cataract progression (β = -0.0002, P = 0.01 and β = -0.001, P = 0.03, respectively), whereas manganese and intake of micronutrient supplements were protective against nuclear cataract at baseline only (β = -0.009, P = 0.03 and β = -0.03, P = 0.01, respectively). CONCLUSIONS: Genetic factors explained 35% of the variation in progression of nuclear cataract over a 10-year period. Environmental factors accounted for the remaining variance, and in particular, dietary vitamin C protected against cataract progression assessed approximately 10 years after baseline

Effectiveness of Two Different Fluoride-Based Agents in the Treatment of Dentin Hypersensitivity: A Prospective Clinical Trial

Hyperesthesia is related to increased sensitivity of dental tissues to mechanical, chemical and thermal stimuli. The aim of this prospective clinical trial was to compare the effectiveness of a calcium-fluoride-forming agent (Tiefenfluorid®, Humanchemie GmbH, Alfeld, Germany) with that of a fluoride varnish (Enamelast™, Ultradent Inc., Cologne, Germany) in the treatment of dental hyperesthesia in adult patients. In total, 176 individuals (106 females and 70 males, aged 18–59 years old) diagnosed with dental hyperesthesia (DH) were enrolled. The main clinical symptoms were hyperesthesia from coldness and sweetness during chewing; the types of clinical lesions were also determined and recorded. The patients were selected randomly and divided into two groups: (i) the first group of 96 patients was treated with Tiefenfluorid® applied in three appointments at 7-day intervals; (ii) the second group of 80 patients was treated with Enamelast™, applied seven times at 7-day intervals. All the patients were recalled 7 days, 14 days, 1 month, 3 months, and 6 months from the last application. At the baseline and during every follow-up visit, the DH was measured with a pulp tester. A random intercept/random slope model was used to evaluate the effect of the treatment, at various times with respect to the initial diagnosis. Within the limits of the present study, Tiefenfluorid® was more effective than Enamelast™ against DH in that it provided long-lasting results, with a significant improvement still detected at the latest 6-month follow-up

Genome-wide association study of primary open-angle glaucoma in continental and admixed African populations.

Primary open angle glaucoma (POAG) is a complex disease with a major genetic contribution. Its prevalence varies greatly among ethnic groups, and is up to five times more frequent in black African populations compared to Europeans. So far, worldwide efforts to elucidate the genetic complexity of POAG in African populations has been limited. We conducted a genome-wide association study in 1113 POAG cases and 1826 controls from Tanzanian, South African and African American study samples. Apart from confirming evidence of association at TXNRD2 (rs16984299; OR[T] 1.20; P = 0.003), we found that a genetic risk score combining the effects of the 15 previously reported POAG loci was significantly associated with POAG in our samples (OR 1.56; 95% CI 1.26-1.93; P = 4.79 × 10-5). By genome-wide association testing we identified a novel candidate locus, rs141186647, harboring EXOC4 (OR[A] 0.48; P = 3.75 × 10-8), a gene transcribing a component of the exocyst complex involved in vesicle transport. The low frequency and high degree of genetic heterogeneity at this region hampered validation of this finding in predominantly West-African replication sets. Our results suggest that established genetic risk factors play a role in African POAG, however, they do not explain the higher disease load. The high heterogeneity within Africans remains a challenge to identify the genetic commonalities for POAG in this ethnicity, and demands studies of extremely large size

Mapping Early Childhood Caries Prevention Programmes in Scotland and South-Eastern Europe

Background: Early Childhood Caries (ECC) is a recognised global public health challenge, and the World Health Organisation (WHO) has set out preventive approaches in an implementation manual. Scotland has an established information-sharing partnership with countries in South-Eastern Europe, where the ECC burden is substantial. Aim: This project aimed to map ECC and preventive programmes in Scotland and South-Eastern Europe against WHO criteria and to facilitate discussion, drawing from recent research and assessment of international consensus, to agree on priority interventions. Methods: A dedicated pro-forma gathered structured information on: population statistics; disease burden; workforce capacity; interventions in dental practice, early years education and the community. A recorded online workshop involved presentations and discussions of policy and practice in relation to current and future ECC prevention plans. Workshop discussions were transcribed and analysed using thematic theory-based implementation frameworks, facilitated by QSR NVivo12.0 software. Results: Data were received from Albania, Bulgaria, Croatia, Romania, Scotland and Serbia. The child population and birth rate are generally declining. In 2019, ECC prevalence among 5–6-year-olds was 80% to 84% in South-Eastern Europe countries, while in Scotland, less than a third (26%) of those children had obvious decay experience in their primary teeth in 2020, compared with more than half (55%) in 2003. A key barrier for implementing ECC prevention is a lack of political prioritisation and funding. Further barriers identified included a lack of integration of public and private preventive programmes, low engagement of professional dental associations, and a lack of population knowledge/awareness of the issue. Implementation might be facilitated through wider universal child health initiatives (e.g. vaccination and maternal health programmes). Conclusion: Mapping disease and oral health prevention activities in Scotland and South-Eastern Europe has allowed for assessment of progress and identified barriers and facilitators for future implementation in line with WHO ECC prevention guidelines

A commonly occurring genetic variant within the NPLOC4–TSPAN10–PDE6G gene cluster is associated with the risk of strabismus

Strabismus refers to an abnormal alignment of the eyes leading to the loss of central binocular vision. Concomitant strabismus occurs when the angle of deviation is constant in all positions of gaze and often manifests in early childhood when it is considered to be a neurodevelopmental disorder of the visual system. As such, it is inherited as a complex genetic trait, affecting 2-4% of the population. A genome-wide association study (GWAS) for self-reported strabismus (1345 cases and 65,349 controls from UK Biobank) revealed a single genome-wide significant locus on chromosome 17q25. Approximately 20 variants across the NPLOC4-TSPAN10-PDE6G gene cluster and in almost perfect linkage disequilibrium (LD) were most strongly associated (lead variant: rs75078292, OR = 1.26, p = 2.24E-08). A recessive model provided a better fit to the data than an additive model. Association with strabismus was independent of refractive error, and the degree of association with strabismus was minimally attenuated after adjustment for amblyopia. The association with strabismus was replicated in an independent cohort of clinician-diagnosed children aged 7 years old (116 cases and 5084 controls; OR = 1.85, p = 0.009). The associated variants included 2 strong candidate causal variants predicted to have functional effects: rs6420484, which substitutes tyrosine for a conserved cysteine (C177Y) in the TSPAN10 gene, and a 4-bp deletion variant, rs397693108, predicted to cause a frameshift in TSPAN10. The population-attributable risk for the locus was approximately 8.4%, indicating an important role in conferring susceptibility to strabismus

Author Correction: Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases.

Emmanuelle Souzeau, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this Article. This has now been corrected in both the PDF and HTML versions of the Article

Associations with photoreceptor thickness measures in the UK Biobank.

Spectral-domain OCT (SD-OCT) provides high resolution images enabling identification of individual retinal layers. We included 32,923 participants aged 40-69 years old from UK Biobank. Questionnaires, physical examination, and eye examination including SD-OCT imaging were performed. SD OCT measured photoreceptor layer thickness includes photoreceptor layer thickness: inner nuclear layer-retinal pigment epithelium (INL-RPE) and the specific sublayers of the photoreceptor: inner nuclear layer-external limiting membrane (INL-ELM); external limiting membrane-inner segment outer segment (ELM-ISOS); and inner segment outer segment-retinal pigment epithelium (ISOS-RPE). In multivariate regression models, the total average INL-RPE was observed to be thinner in older aged, females, Black ethnicity, smokers, participants with higher systolic blood pressure, more negative refractive error, lower IOPcc and lower corneal hysteresis. The overall INL-ELM, ELM-ISOS and ISOS-RPE thickness was significantly associated with sex and race. Total average of INL-ELM thickness was additionally associated with age and refractive error, while ELM-ISOS was additionally associated with age, smoking status, SBP and refractive error; and ISOS-RPE was additionally associated with smoking status, IOPcc and corneal hysteresis. Hence, we found novel associations of ethnicity, smoking, systolic blood pressure, refraction, IOPcc and corneal hysteresis with photoreceptor thickness