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STUDY QUESTION Is there an association between low-to-moderate levels of prenatal alcohol exposure (PAE) and children's facial shape? SUMMARY ANSWER PAE before and during pregnancy, even at low level (<12 g of alcohol per week), was found associated with the facial shape of children, and these associations were found attenuated as children grow older. WHAT IS KNOWN ALREADY High levels of PAE during pregnancy can have significant adverse associations with a child's health development resulting in recognizably abnormal facial development. STUDY DESIGN, SIZE, DURATION This study was based on the Generation R Study, a prospective cohort from fetal life onwards with maternal and offspring data. We analyzed children 3-dimensional (3D) facial images taken at ages 9 (n = 3149) and 13 years (n = 2477) together with the data of maternal alcohol consumption. PARTICIPANTS/MATERIALS, SETTING, METHODS We defined six levels of PAE based on the frequency and dose of alcohol consumption and defined three tiers based on the timing of alcohol exposure of the unborn child. For the image analysis, we used 3D graph convolutional networks for non-linear dimensionality reduction, which compressed the high-dimensional images into 200 traits representing facial morphology. These 200 traits were used for statistical analysis to search for associations with PAE. Finally, we generated heatmaps to display the facial phenotypes associated with PAE. MAIN RESULTS AND THE ROLE OF CHANCE The results of the linear regression in the 9-year-old children survived correction for multiple testing with false discovery rate (FDR). In Tier 1 where we examined PAE only before pregnancy (exposed N = 278, unexposed N = 760), we found three traits survived FDR correction. The lowest FDR- P is 1.7e–05 (beta = 0.021, SE = 0.0040) in Trait #29; In Tier 2b where we examine any PAE during first trimester (exposed N = 756; unexposed N = 760), we found eight traits survived FDR correction. The lowest FDR- P is 9.0e−03 (beta = −0.013, SE = 0.0033) in Trait #139. Moreover, more statistically significant facial traits were found in higher levels of PAE. No FDR-significant results were found in the 13-year-old children. We map these significant traits back to the face, and found the most common detected facial phenotypes included turned-up nose tip, shortened nose, turned-out chin, and turned-in lower-eyelid-related regions. LIMITATIONS, REASONS FOR CAUTION We had no data for alcohol consumption more than three months prior to pregnancy and thus do not know if maternal drinking had chronic effects. The self-reported questionnaire might not reflect accurate alcohol measurements because mothers may have denied their alcohol consumption. WIDER IMPLICATIONS OF THE FINDINGS Our results imply that facial morphology, such as quantified by the approach we proposed here, can be used as a biomarker in further investigations. Furthermore, our study suggests that for women who are pregnant or want to become pregnant soon, should quit alcohol consumption several months before conception and completely during pregnancy to avoid adverse health outcomes in the offspring. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by Erasmus Medical Centre, Rotterdam, the Erasmus University Rotterdam, and the Netherlands Organization for Health Research. V.W.V.J. reports receipt of funding from the Netherlands Organization for Health Research (ZonMw 90700303). W.J.N. is a founder, a scientific lead, and a shareholder of Quantib BV. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Solar neutrinos have been pivotal to the discovery of neutrino flavour oscillations and are a unique tool to probe the reactions that keep the Sun shine. Although most of solar neutrino components have been directly measured, the neutrinos emitted by the keystone pp reaction, in which two protons fuse to make a deuteron, have so far eluded direct detection. The Borexino experiment, an ultra–pure liquid scintillator detector running at the Laboratori Nazionali del Gran Sasso in Italy, has now filled the gap, providing the first direct real time measurement of pp neutrinos and of the solar neutrino luminosity.

Background: The severity of facial telangiectasia or red veins is associated with many lifestyle factors. However, the genetic predisposition remains unclear. Objectives: We performed a genome‐wide association study (GWAS) on facial telangiectasia in the Rotterdam Study (RS) and tested for replication in two independent cohorts. Additionally, a candidate gene approach with known pigmentation genes was performed. Methods: Facial telangiectasia were extracted from standardized facial photographs (collected from 2010–2013) of 2842 northwestern European participants (median age 66.9, 56.8% female) from the RS. Our GWAS top hits (P‐value <10−6) were tested for replication in 460 elderly women of the SALIA cohort and in 576 additional men and women of the RS. Associations of top single nucleotide polymorphisms (SNPs) with expression quantitative trait loci (eQTL) in various tissues were reviewed (GTEx database) alongside phenotype associations in the UK biobank database. SNP‐based associations between known pigmentation genes and facial telangiectasia were tested. Conditional analysis on skin colour was additionally performed. Results: Our most significant GWAS signal was rs4417318 (P‐value 5.38*10−7), an intergenic SNP on chromosome 12 mapping to the SLC16A7 gene. Other suggestive SNPs tagged genes ZNF211, ZSCAN4, ICOS and KCNN3; SNP eQTLs and phenotype associations tagged links to the vascular system. However, the top signals did not pass significance in the two replication cohorts. The pigmentation genes KIAA0930, SLCA45A2 and MC1R, were significantly associated with telangiectasia in a candidate gene approach but not independently of skin colour. Conclusion: In this GWAS on telangiectasia in a northwestern European population, no genome‐wide significant SNPs were found, although suggestive signals indicate genes involved in the vascular system might be involved in telangiectasia. Significantly associated pigmentation genes underline the link between skin colour and telangiectasia. [ABSTRACT FROM AUTHOR]

Summary: Background: The underlying phenotypic correlations between wrinkles, pigmented spots (PS), telangiectasia and other related facial‐ageing subphenotypes are not well understood. Objectives: To analyse the underlying phenotypic correlation structure between seven features for facial ageing: global wrinkling, perceived age (PA), Griffiths photodamage grading, PS, telangiectasia, actinic keratosis (AK) and keratinocyte cancer (KC). Methods: This was a cross‐sectional study. Facial photographs and a full‐body skin examination were used. We used principal component analysis (PCA) to derive principal components (PCs) of common variation between the features. We performed multivariable linear regressions between age, sex, body mass index, smoking and ultraviolet radiation exposure and the PC scores derived from PCA. We also tested the association between the main PC scores and 140 single‐nucleotide polymorphisms (SNPs) previously associated with skin‐ageing phenotypes. Results: We analysed data from 1790 individuals with complete data on seven features of skin ageing. Three main PCs explained 73% of the total variance of the ageing phenotypes: a hypertrophic/wrinkling component (PC1: global wrinkling, PA and Griffiths grading), an atrophic/skin colour component (PC2: PS and telangiectasia) and a cancerous component (PC3: AK and KC). The associations between lifestyle and host factors differed per PC. The strength of SNP associations also differed per component with the most SNP associations found with the atrophic component [e.g. the IRF4 SNP (rs12203592); P‐value = 1·84 × 10–22]. Conclusions: Using a hypothesis‐free approach, we identified three major underlying phenotypes associated with extrinsic ageing. Associations between determinants for skin ageing differed in magnitude and direction per component. What's already known about this topic? Facial ageing is a complex phenotype consisting of different features including wrinkles, pigmented changes, telangiectasia and cancerous‐related growths; it is not clear how these phenotypes are related to each other and to other phenotypes.A few studies have described two main clinical phenotypes for photoageing, namely hypertrophic ageing and atrophic ageing, which have been based solely on the clinical assessment of photoageing characteristics. What does this study add? We are the first to use epidemiology data to identify three main components associated with photoageing, namely a hypertrophic component (global wrinkling; perceived age; Griffiths grading) and atrophic component (pigmented spots; telangiectasia) and a cancer component (actinic keratosis; keratinocyte cancer).Association analysis showed different effects and direction of environmental determinants and genetic associations with the three components, with the most significant gene variants associations found for the atrophic component. Linked Comment:Law. Br J Dermatol 2020; 182:1323–1324. Plain language summary available online [ABSTRACT FROM AUTHOR]

Background: Telangiectasia or red veins are one of the prominent features of facial skin ageing. To date, there are few studies investigating the determinants of telangiectasia. Objectives: We investigated lifestyle and physiological factors associated with facial telangiectasia in a large prospective Dutch cohort study. Methods: Telangiectasia was quantified digitally from standardized facial photographs of 2842 North European participants (56.8% female, median age 66.9) from the Rotterdam Study, collected in 2010–2013. Effect estimates from multivariable linear regressions are presented as the percentage difference in the mean value of telangiectasia area per unit increase of a determinant (%Δ) with corresponding 95% CI. Results: Significant determinants were older age [1.7%Δ per year (95% CI 1.4, 2.0)], female sex [18.3%Δ (95% CI 13.2, 23.6)], smoking [current versus never 38.4%Δ (95% CI 30.3, 47.0); former versus never 11.6%Δ (95% CI 6.6, 16.9)], a high susceptibility to sunburn [10.2%Δ (95% CI 5.4, 15.3)] and light skin colour [pale versus white‐to‐olive 31.4%Δ (95% CI 19.7, 44.1]; white vs. white‐to‐olive 9.2%Δ (95% CI 2.8, 16.0)]. Conclusions: In this large cohort study, we confirmed known and described new determinants of facial telangiectasia. [ABSTRACT FROM AUTHOR]