Trans-ancestral genome-wide association study of longitudinal pubertal height growth and shared heritability with adult health outcomes.

BACKGROUND: Pubertal growth patterns correlate with future health outcomes. However, the genetic mechanisms mediating growth trajectories remain largely unknown. Here, we modeled longitudinal height growth with Super-Imposition by Translation And Rotation (SITAR) growth curve analysis on ~ 56,000 trans-ancestry samples with repeated height measurements from age 5 years to adulthood. We performed genetic analysis on six phenotypes representing the magnitude, timing, and intensity of the pubertal growth spurt. To investigate the lifelong impact of genetic variants associated with pubertal growth trajectories, we performed genetic correlation analyses and phenome-wide association studies in the Penn Medicine BioBank and the UK Biobank. RESULTS: Large-scale growth modeling enables an unprecedented view of adolescent growth across contemporary and 20th-century pediatric cohorts. We identify 26 genome-wide significant loci and leverage trans-ancestry data to perform fine-mapping. Our data reveals genetic relationships between pediatric height growth and health across the life course, with different growth trajectories correlated with different outcomes. For instance, a faster tempo of pubertal growth correlates with higher bone mineral density, HOMA-IR, fasting insulin, type 2 diabetes, and lung cancer, whereas being taller at early puberty, taller across puberty, and having quicker pubertal growth were associated with higher risk for atrial fibrillation. CONCLUSION: We report novel genetic associations with the tempo of pubertal growth and find that genetic determinants of growth are correlated with reproductive, glycemic, respiratory, and cardiac traits in adulthood. These results aid in identifying specific growth trajectories impacting lifelong health and show that there may not be a single "optimal" pubertal growth pattern.

Accommodative-vergence disorders in a paediatric ophthalmology clinical setting in Argentina.

PURPOSE: To determine the frequency of potential non-strabismic accommodative-vergence anomalies (NSAVA) and investigate associations between NSAVA, refractive errors and age among children attending a paediatric ophthalmology clinic. METHODS: This study included children and adolescents aged 5-19 years attending an ophthalmology clinic with at least two follow-up visits. At their first visit, children had a comprehensive ophthalmic examination, including refractive error measurement by cycloplegic autorefraction and spectacles were prescribed if necessary. At the second visit, children had an examination of best-corrected visual acuity, convergence and accommodation to identify potential NSAVA. The relationship between age, sex, heterophoria and refractive error and potential NSAVA was assessed by a multivariable logistic regression model. RESULTS: A total of 384 children and adolescents were evaluated. Their mean age was 10.97 ± 3.07 years and 58.9% were females. Forty-two per cent of children failed the NSAVA tests and 34.1% had myopia (≤-0.50 D). Children who failed NSAVA tests self-reported a higher proportion of reading problems (73.7%) compared to those who passed the tests (26.3%; p < 0.001). Children with self-reported reading problems were more likely to have accommodative infacility (57.9%) compared with children without (42.1%; p < 0.001). Refractive error and age were not associated with failure in NSAVA tests (p > 0.05). CONCLUSIONS: NSAVA was a frequent cause of vision problems found in a sample of children from an ophthalmology paediatric clinic. Thus, further research is necessary to understand the potential of public health policies to prevent, refer, diagnose and treat those conditions.

Family-focused contextual factors associated with lifestyle patterns in young children from two mother-offspring cohorts: GUSTO and EDEN.

BACKGROUND: Integrated patterns of energy balance-related behaviours of preschool children in Asia are sparse, with few comparative analyses. PURPOSE: Using cohorts in Singapore (GUSTO) and France (EDEN), we characterized lifestyle patterns of children and investigated their associations with family-focused contextual factors. METHODS: Ten behavioural variables related to child's diet, walking, outdoor play and screen time were ascertained by parental questionnaires at age 5-6 years. Using principal component analysis, sex-specific lifestyle patterns were derived independently for 630 GUSTO and 989 EDEN children. Contextual variables were organised into distal (family socio-economics, demographics), intermediate (parental health, lifestyle habits) and proximal (parent-child interaction factors) levels of influence and analysed with hierarchical linear regression. RESULTS: Three broadly similar lifestyle patterns were identified in both cohorts: "discretionary consumption and high screen time", "fruit, vegetables, and low screen time" and "high outdoor playtime and walking". The latter two patterns showed small differences between cohorts and sexes. The "discretionary consumption and high screen time" pattern was consistently similar in both cohorts; distal associated factors were lower maternal education (EDEN boys), no younger siblings (GUSTO boys) and Malay/Indian ethnicity (GUSTO), while intermediate and proximal associated factors in both cohorts and sexes were poor maternal diets during pregnancy, parents allowing high child control over food intake, snacking between meals and having television on while eating. CONCLUSIONS: Three similar lifestyle patterns were observed among preschool children in Singapore and France. There were more common associated proximal factors than distal ones. Cohort specific family-focused contextual factors likely reflect differences in social and cultural settings. Findings will aid development of strategies to improve child health.

Light and myopia: from epidemiological studies to neurobiological mechanisms.

Myopia is far beyond its inconvenience and represents a true, highly prevalent, sight-threatening ocular condition, especially in Asia. Without adequate interventions, the current epidemic of myopia is projected to affect 50% of the world population by 2050, becoming the leading cause of irreversible blindness. Although blurred vision, the predominant symptom of myopia, can be improved by contact lenses, glasses or refractive surgery, corrected myopia, particularly high myopia, still carries the risk of secondary blinding complications such as glaucoma, myopic maculopathy and retinal detachment, prompting the need for prevention. Epidemiological studies have reported an association between outdoor time and myopia prevention in children. The protective effect of time spent outdoors could be due to the unique characteristics (intensity, spectral distribution, temporal pattern, etc.) of sunlight that are lacking in artificial lighting. Concomitantly, studies in animal models have highlighted the efficacy of light and its components in delaying or even stopping the development of myopia and endeavoured to elucidate possible mechanisms involved in this process. In this narrative review, we (1) summarize the current knowledge concerning light modulation of ocular growth and refractive error development based on studies in human and animal models, (2) summarize potential neurobiological mechanisms involved in the effects of light on ocular growth and emmetropization and (3) highlight a potential pathway for the translational development of noninvasive light-therapy strategies for myopia prevention in children.

Blurred digital mammography images: an analysis of technical recall and observer detection performance.

OBJECTIVE: Blurred images in full-field digital mammography are a problem in the UK Breast Screening Programme. Technical recalls may be due to blurring not being seen on lower resolution monitors used for review. This study assesses the visual detection of blurring on a 2.3-MP monitor and a 5-MP report grade monitor and proposes an observer standard for the visual detection of blurring on a 5-MP reporting grade monitor. METHODS: 28 observers assessed 120 images for blurring; 20 images had no blurring present, whereas 100 images had blurring imposed through mathematical simulation at 0.2, 0.4, 0.6, 0.8 and 1.0 mm levels of motion. Technical recall rate for both monitors and angular size at each level of motion were calculated. χ2 tests were used to test whether significant differences in blurring detection existed between 2.3- and 5-MP monitors. RESULTS: The technical recall rate for 2.3- and 5-MP monitors are 20.3% and 9.1%, respectively. The angular size for 0.2- to 1-mm motion varied from 55 to 275 arc s. The minimum amount of motion for visual detection of blurring in this study is 0.4 mm. For 0.2-mm simulated motion, there was no significant difference [χ2 (1, N = 1095) = 1.61, p = 0.20] in blurring detection between the 2.3- and 5-MP monitors. CONCLUSION: According to this study, monitors ≤2.3 MP are not suitable for technical review of full-field digital mammography images for the detection of blur. Advances in knowledge: This research proposes the first observer standard for the visual detection of blurring.