Cell-type-specific regulation of gene expression plays a central role in complex disease etiology, yet most transcriptome-wide association studies (TWAS) rely on bulk tissue models. Recently, a couple methods leverage single-cell transcriptomics to perform TWAS at the cell-type resolution, but they are limited by scarce matched genotype-single-cell cohorts and restricted to peripheral blood, with minimal coverage of less accessible, disease-relevant tissues. In this study, we developed S-MiXcan, a summary-statistics-based TWAS framework that enables cell-type-aware association analysis using bulk transcriptomic data across K ≥ 2 cell types without requiring individual-level data. As a major advancement over our prior tool MiXcan, S-MiXcan jointly models genetically regulated expression (GReX) across K cell types, accounts for cross-cell-type correlations, identifies disease-associated genes, and provides probabilistic interpretations for distinguishing cell-type-specific from shared associations. In real data analyses, compared with using individual-level genotype-based implementation, S-MiXcan achieved highly concordant results (Pearson`s r ≈ 1) in cell-type-aware TWAS. Applied to large-scale multi-cohort Genome-Wide Association Study (GWAS) meta-analyses from the Breast Cancer Association Consortium, S-MiXcan maintained well-controlled type I error (genomic inflation λ = 1.057), identified key breast cancer risk associated genes that function in a cell-type specific manner, and revealed relevant cell types through probabilistic inference. These results demonstrate that S-MiXcan, publicly available at https://github.com/songxiaoyu/SMiXcan, provides a scalable and interpretable framework for cell-type-aware TWAS. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by Singapore Ministry of Education (MOE) FY2024-MOET1- 0004, Ministry of Health (MOH) Duke-NUS Signature Research Programme, and Na- tional Medical Research Council (NMRC) CS-IRG CIRG25jul-0023. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study used only publicly available human data. GTEx data are available from GTEx v8 (dbGaP accession number phs000424.v8.p2 (https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study\_id=phs000424.v8.p2). Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) data are available from dbGaP accession number phs001265.v1.p1 (https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study\_id=phs001265.v1.p1). Breast cancer risk GWAS summary statistics are available from https://www.ccge.medschl.cam.ac.uk/breast-cancer-association-consortium-bcac/data-data-access/summary-results/gwas-summary-associations. The 1000 Genomes Project Phase 3 reference data are available at https://www.internationalgenome.org/cate. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes S-MiXcan software, documentation, and tutorial are open-source at https://github.com/songxiaoyu/SMiXcan. The data used in this study are publicly available. GTEx data are available from GTEx v8 (dbGaP accession number phs000424.v8.p2 (https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study\_id=phs000424.v8.p2). Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) data are available from dbGaP accession number phs001265.v1.p1 (https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study\_id=phs001265.v1.p1). Breast cancer risk GWAS summary statistics are available from https://www.ccge.medschl.cam.ac.uk/breast-cancer-association-consortium-bcac/data-data-access/summary-results/gwas-summary-associations. The 1000 Genomes Project Phase 3 reference data are available at https://www.internationalgenome.org/cate.

Given the genetic predisposition to myopia, polygenic risk scores (PRS) have been proposed as a tool for early risk identification. This study assessed the discriminatory ability of PRS in myopia prediction systematically and compared the performance of different PRS models. This systematic review followed PRISMA guidelines and was preregistered in PROSPERO (CRD420251180577). Five databases (PubMed, Web of Science, Cochrane Library, EMBASE and Scopus) were searched from inception to October 11, 2025. Eligible studies were required to develop or validate myopia prediction models that incorporated PRS and to report at least one discrimination metric. The methodological quality and risk of bias were assessed independently using the Prediction Model Risk of Bias Assessment Tool (PROBAST). Ten studies met the inclusion criteria. The discriminatory performance of PRS-only models ranged from an area under the receiver operating characteristic curve (AUC) of 0.51–0.80, whereas combined models integrating PRS with clinical or other factors demonstrated a higher performance range (AUC 0.57–0.99). Predictive performance varied according to myopia phenotype, ancestry, and PRS construction strategy. Models tended to achieve stronger discrimination for high or moderate myopia compared with low myopia, and performed better in European populations than in other ancestry groups. Increasing the number of single-nucleotide polymorphisms included in the PRS yielded only modest incremental improvements in predictive accuracy. Across all comparisons, combined models consistently outperformed PRS-only models. PRS contributes to myopia risk prediction, particularly when integrated with clinical or other risk factors, and its predictive performance varies across myopia phenotype, ethnicity, age and the number of single-nucleotide polymorphisms. Further large-scale, multi-ancestry validation and evaluation of implementation feasibility are needed before PRS can be incorporated effectively into routine myopia prevention and risk stratification strategies.

To evaluate the rate and determinants of visual field (VF) progression across different severities of primary angle-closure glaucoma (PACG). Chinese patients with PACG who had ≥ 5 reliable VFs and ≥ 5 years of follow-up were included. Disease severity was classified by baseline mean deviation (MD) as mild (≥-6.0dB), moderate (-6.01 to -12.0dB) or severe (<-12.0dB). VF progression was categorized as slow (>-0.25dB/year), intermediate (-0.25 to -1.0dB/year), or fast (≤-1.0dB/year). Among 783 patients evaluated, 477 met the inclusion criteria: 140 (29.4%) mild, 161 (33.8%) moderate, and 176 (36.9%) severe PACG. Most eyes showed slow progression (n = 248, 52.0%), followed by intermediate (n = 164, 34.4%) and fast (n = 65, 13.6%). Moderate PACG progressed fastest (-0.45 ± 0.80dB/year), compared with mild (-0.39 ± 0.54dB/year) and severe disease (-0.12 ± 1.12dB/year) (p < 0.001), demonstrating a U-shaped relationship between disease severity and progression. In mild PACG, a longer interval to cataract surgery was associated with reduced odds of slow progression (OR, 0.90; 95% CI, 0.81-1.00, p = 0.05). In moderate PACG eyes, females and poorer presenting visual acuity were associated with slow progression (OR, 3.12; 95% CI, 1.33–7.72; p = 0.01 and OR, 5.54; 95% CI, 1.37–26.50; p = 0.02 respectively). In severe PACG, females and higher presenting IOP were associated with slow progression (OR, 2.63; 95% CI, 1.20–5.97; p = 0.02 and OR, 1.06; 95% CI, 1.01–1.11; p = 0.02 respectively). VF progression in PACG patients demonstrated a U-shaped relationship with disease severity, with moderate PACG exhibiting the fastest progression. Determinants of progression differed for different severities of PACG, highlighting the importance of stage-specific treatment of PACG.

AIMS:The impact of genetic variants on high myopia (HM) remains unclear. This study aims to systematically evaluate the relationship between genetic polymorphisms and HM. METHODS:Eligible studies were retrieved from five databases (PubMed, Web of Science, Cochrane, Embase and Scopus) up to 18 January 2025. We included all case-control studies that examined the association of single nucleotide polymorphisms (SNPs) with HM susceptibility. Fixed or random effects models were used to evaluate pooled ORs and CIs for each SNP in HM. Sensitivity analyses were conducted to assess the reliability and stability of the results. RESULTS:Seventy-six studies (89 separate cohorts) were eligible for the meta-analysis of HM, involving 77 SNPs in 34 genes. Twenty-two SNPs in 13 genes (rs1516794 in ACAN gene; rs2269336 in COL1A1 gene; rs2071861 and rs2009066 in CRYBA4 gene; rs339501 in FGF10 gene; rs698047 in HIVEP3 gene; rs3741834, rs2300588, rs3759223 and rs7135740 in LUM gene; rs9318086 in MIPEP gene; rs243845 and rs1861320 in MMP2 gene; rs662702 and rs644242 in PAX6 gene; rs8027411 and rs17175798 in RASGRF1 gene; rs7839488, rs4395927 and rs6469937 in SNTB1 gene; rs1800470 in TGFβ1 gene; and rs7829127 in ZMAT4 gene) showed significant associations with HM. CONCLUSION:This study identified 22 SNPs in 13 genes (ACAN, COL1A1, CRYBA4, FGF10, HIVEP3, LUM, MIPEP, MMP2, PAX6, RASGRF1, SNTB1, TGFβ1 and ZMAT4) as potential genetic biomarkers for HM. Future research should conduct large-scale genome-wide association studies across diverse populations to yield more robust evidence.

Purpose:To evaluate shared genetic influences and investigate the association of chronic kidney disease (CKD) with the risk for advanced age-related macular degeneration (AMD). Design:Prospective cohort study and 2-sample Mendelian randomization (MR) analyses. Participants:Data from 430 016 participants in the UK Biobank cohort and summary statistics from the largest publicly available genome-wide association studies on estimated glomerular filtration rate (eGFR) (n = 1 004 040) and advanced AMD (n = 33 976; 16 144 cases) were analyzed. Methods:Cox regression models were used to assess the association between CKD and incident AMD, adjusting for demographic, lifestyle, and clinical covariates. For MR analyses, we used the random-effects inverse-variance weighted model as the primary model, supported by 5 additional MR models for sensitivity analyses. A causal relationship was considered significant if P < 0.05 in the primary model and in ≥2 sensitivity models, with all MR models showing a consistent effect direction. Colocalization analysis was performed to further identify shared genetic loci linking CKD and AMD. Main Outcome Measures:Causal associations between eGFR and advanced AMD. Results:In the UK Biobank, baseline CKD was significantly associated with an increased risk of incident AMD (hazard ratio, 1.12; 95% confidence interval [CI], 1.01-1.25; P = 0.035) over a 10-year follow-up. Mendelian randomization analyses also demonstrated causality between lower eGFR and higher risk of advanced AMD (odds ratio, 2.03; 95% CI, 1.01-4.08; P = 0.048). Colocalization analysis indicated that the apolipoprotein E gene may contribute to this causality (rs56131196; colocalization posterior probability = 1.00, P = 2.29 x 10-33 for AMD; P = 2.29 x 10-13 for eGFR). Conclusions:Both prospective cohort and MR analyses support causality between CKD and AMD, highlighting the need for AMD screening among patients with CKD. Financial Disclosures:Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

The global prevalence of myopia and pathologic myopia (PM) has dramatically increased, raising significant public health concerns due to associated vision-threatening complications, such as myopic maculopathy (MM). This comprehensive review integrates the latest evidence regarding the environmental, genetic, and epigenetic factors contributing to myopia, as well as recent advances in precision medicine and therapeutic approaches aimed at mitigating the disease's impact. We examine how environmental factors interact with polygenic risk factors and epigenetic changes to influence disease progression. The application of artificial intelligence (AI) enhances the integration of genomic, environmental, and clinical data, thereby improving risk assessment and personalizing treatment options. Therapeutic strategies, including the use of low-dose atropine, orthokeratology, and repeated low-level red-light therapy, have shown promise in controlling myopia. Furthermore, emerging gene-editing techniques are being developed, although they are unlikely to be implemented as treatments for myopia and PM in the near future. Despite these advancements, disparities in resource availability and the implementation of interventions continue to hinder global equity, underscoring the need for scalable solutions such as mobile health applications and community-based preventive programs. This review emphasizes the importance of interdisciplinary collaboration to merge precision medicine with public health strategies, ensuring that scientific breakthroughs are equitably translated into clinical care. By aligning environmental preventive measures, genetic discoveries, and AI-powered innovations, this review outlines a strategic plan for reducing the global burden of myopia and its complications.

With the advance of next-generation sequencing, various gene-based rare variant association tests have been developed, particularly for binary and continuous phenotypes. In contrast, fewer methods are available for traits not following binomial or normal distributions. To address this, we previously proposed a set of burden- and kernel-based rare variant tests for count data following zero-inflated Poisson (ZIP) distributions, referred to as ZIP-b and ZIP-k tests. We sought to extend the methods to accommodate negative binomial distribution and implemented these tests in a new R package. We introduce ZIM4rv, an R package designed to analyze the association of rare variants with zero-inflated counts outcomes. Our package offers two novel models developed by our team: our previously proposed ZIP-b and ZIP-k tests, and the newly derived Negative Binomial Burden and Kernel Test (ZINB-b, ZINB-k). Additionally, we include an ad-hoc two-stage analysis, testing zero and non-zero as a binary outcome and non-zero as a continuous outcome, respectively. To showcase the utility of our platform, we applied this program to analyze neuritic plaque count data from the ROSMAP cohort. The R package ZIM4rv presents an integrated workflow for conducting association tests on a set of rare variants with zero-inflated counts data.

Age and genetic predisposition are well-known, non-modifiable risk factors for Alzheimer’s disease (AD). Epidemiological studies have linked several modifiable risk factors to AD, but less is known about their influence on the age-at-onset (AAO) of AD. With an increase of genome-wide association studies (GWASs) and advanced genetic analysis developed, we sought to identify modifiable risk factors for AAO of AD and evaluate their causal effects. For AAO of AD, we utilized pooled genome-wide imputed genotype data from 9,219 AD cases and 10,345 controls from 20 cohorts of the Alzheimer Disease Genetics Consortium (ADGC) and our own GWAS summary statistics for AAO of AD (Li et al. 2023). Thirty-eight exposure factors related to comorbidity, lifestyle, and psychosocial risk factors were screened. The GWAS summary statistics of these exposures were from results released by individual publications or IEU OpenGWAS projects. PRSice-2 was used to construct polygenic scores (PGS) for each exposure in ADGC subjects. Linear mixed models (LMM) were used to test for association of the exposure-PGS with AAO, adjusting for sex, APOE-E4, 10 PCs, and a random intercept by cohort. Exposures meeting p< 0.005 were considered significant risk factors, and they were then evaluated for the causal effect on AAO of AD by a two-sample Mendelian Randomization (MR) using GWAS summary statistics of exposures (exposure-GWAS) and AAO of AD. Instrumental variables were selected based on variants meeting p< 5×10 −8 and p<5×10 −6 , respectively, from the exposure-GWAS. We evaluated causal effects by the MR inverse variance weighted method and then followed by sensitivity analyses using weighted median and MR-Egger. Seven genetically inferred exposures via PGS were significantly associated with AAO of AD (p < 0.005), including higher education attainment and relative fat intake delaying AD onset and type 2 diabetes, cardiovascular disease (CVD), hypertension, and smoking leading to earlier AAO. MR analysis showed lower education, T2D, CVD, and hypertension with significant causal effects on shifting AAO earlier (p<0.007). The seven modifiable risk factors, particularly, the four causal factors for AAO of AD, will facilitate the early intervention and provide targets to delay AD onset.

center dot PURPOSE: Animal models suggest omega-3 polyunsaturated fatty acids (PUFAs) may protect against myopia by modulating choroidal blood perfusion, but clinical evidence is scarce and mixed. We aimed to determine the causality between omega-3 PUFAs and myopia using Mendelian randomization (MR) analysis. center dot DESIGN: Two-sample MR analysis. center dot METHODS: Exposures are genetically predicted plasma levels of 18 fatty acid (FA)-related traits. Spherical equivalent refraction (SER) and axial length were used as measurements of myopia. Genome-wide association study summary data on plasma levels of 18 FA-related traits (n = 115,006), refractive spherical equivalent (n = 351,091), axial length (n = 69,945), and choroidal thickness (n = 44,823) were sourced from the UK Biobank, the Genetic Epidemiology Research on Adult Health and Aging cohort, and the Consortium for Refractive Error and Myopia Study. We used 5 MR models and considered results statistically significant if the Bonferroni-corrected P value was <= 2.78 x 10-3 in at least 3 MR models. The ,B represents the change in outcomes (SER in diopters; axial length in millimeters; and choroidal thickness in SD) per SD unit increase in FA levels. center dot RESULTS: At a Bonferroni-corrected significance, higher levels of omega-3 ( ,B, 0.32-0.34), omega-3-total FA ratio ( ,B, 0.31-0.44), docosahexaenoic acid (DHA) ( ,B, 0.36-0.46), DHA-total FA ratio ( ,B, 0.37-0.53), PUFA-total FA ratio ( ,B, 0.07-1.003), and degree of unsaturation ( ,B, 0.28-0.44) were associated with a more positive SER, suggesting a lower risk of myopia. Similar trends were observed for axial length albeit with borderline significance ( P <= .035 in >= 2 models). Higher levels of omega-3, DHA, DHA-total FA ratio, PUFA-total FA ratio, PUFA-monounsaturated FA ratio, and degree of unsaturation were nominally associated with thicker choroidal thickness ( ,B, 0.05-0.13; P <= .045 in >= 2 models). center dot CONCLUSION: Our multiple MR models suggest a protective effect of omega-3 and DHA on myopia, potentially through modulation of choroidal blood perfusion. Further randomized clinical trials are needed to confirm the effectiveness and determine the optimal dose and duration. (Am J Ophthalmol 2024;268: 368-377. (c) 2024 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Background Condition-specific measures of Health-Related Quality of Life (HRQoL) are more sensitive than generic tools. Sizing Them Up (STU) is a parent-proxy, obesity-specific HRQoL measure which was found to be reliable and valid internationally, but has yet to be utilised in Singapore. Objectives Our study aims to i) validate STU in adolescents seeking obesity therapy in KK Women’s and Children’s Hospital (KKH); and ii) determine demographic factors associated with STU scores. Methods We recruited 91 adolescents aged between 11 and 17 years old and their parents from KKH between June 2022 and January 2023. Parents completed STU and the generic Pediatric Quality of Life Inventory (PedsQL) upon recruitment, and repeated STU at least 2 weeks later. Results 65% of participants were males, with a mean Body Mass Index (BMI) of 32.3 ± 5.1 kg/m2 and mean age of 13.6 ± 1.8 years old. STU demonstrated strong internal consistency (overall Cronbach’s α = 0.85) and moderate test-retest reliability (intraclass correlation coefficients = 0.30-0.70). There was high correlation between STU scores and i) the adolescents’ BMI; and ii) equivalent domains of PedsQL, suggesting moderate to strong construct and convergent validity respectively. Indian adolescents, lower parental education level and single parents were associated with poorer STU scores. Conclusion STU is a reliable, valid obesity-specific HRQoL measure in a local clinical population of adolescents undergoing obesity therapy, and can help clinicians to understand parents’ impression of the impact of obesity on their child. Knowing the demographic variables associated with STU can enable clinicians to identify adolescents whose HRQoL are disproportionately affected by obesity.

We investigated whether the effect of lipid-lowering drugs (LLDs) on age-related macular degeneration (AMD) differs according to the main complement genetic variants in Singapore Epidemiology of Eye Diseases (SEED) (n = 5,579) and UK Biobank studies (n = 445,727). The effect of LLD was determined for each stratum of 20 complement genetic variants. In SEED, 484 individuals developed AMD and 216 showed progression over 6 years. In the UK Biobank, 913 participants developed AMD over 11 years. rs1061170 variant (complement factor H gene) was the only variant for which we found a protective effect in both populations. This effect was found in individuals carrying at least one C allele in SEED (odds ratio [OR] = 0.41; 95% confidence interval [CI], 0.19-0.87) and in individuals carrying two C alleles in UK Biobank (hazard ratio [HR] = 0.65; 95% CI, 0.45-0.93). These effects corresponded to a 50% and 35% decrease in AMD risk, respectively. Our study highlights the potential for personalized therapy for AMD based on complement genotyping.

INTRODUCTION:There is limited research on the psychosocial health of Asian adolescents undergoing obesity treatment. Our study examined the predictors of psychological distress, disordered eating and poor health-related quality of life (HRQoL) in these adolescents and the associations between them. METHODS:A total of 82 adolescents aged 11-17 years were recruited from the Weight Management Clinic in KK Women's and Children's Hospital between June 2022 and January 2023. Participants completed the following questionnaires: (a) Young Person's Clinical Outcomes in Routine Evaluation (YP-Core) assessing for psychological distress, (b) Children's Eating Attitude Test (ChEAT) evaluating for disordered eating behaviours, and (c) Pediatric Quality of Life Inventory (PedsQL) measuring HRQoL. RESULTS:Participating adolescents had a mean body mass index of 31.9 ± 5.1 kg/m2. Of the participants, 40% reported significantly symptomatic psychological distress (YP-Core score ≥14) and 16% were at risk of eating disorders (ChEAT score ≥20). A higher YP-Core score was the only significant determinant of poorer HRQoL, after controlling for demographic variables and ChEAT scores. Malay (regression coefficient: 6.6, 95% confidence interval [CI]: 0.6-12.6, P = 0.031) and Indian (regression coefficient: 8.9, 95% CI: 3.8-14.0, P = 0.001) adolescents were more likely to report disordered eating and psychological distress, respectively, as compared to Chinese adolescents. Adolescents whose parent(s) had obesity (regression coefficient: 3.4, 95% CI: 0.1-6.7, P = 0.043) were also more likely to experience greater psychological distress. CONCLUSION:Understanding the determinants of psychological distress, disordered eating and HRQoL will facilitate targeted screening and management of the psychosocial complications of adolescent obesity.

PURPOSE:Epidemiologic studies and clinical trials have reported inconsistent findings regarding omega-3 fatty acids' protective role in age-related macular degeneration (AMD). We investigated their association in a prospective cohort and examined causality using Mendelian randomization (MR) analyses. DESIGN:Prospective cohort study and 2-sample MR analyses. PARTICIPANTS:The cohort included 258 350 AMD-free individuals of European descent from the UK Biobank. Mendelian randomization analyses used genome-wide association study data on plasma omega-3 and docosahexaenoic acid (DHA) (UK Biobank, n = 115 006) and AMD (dry, wet, and any; FinnGen, n = 208 690-209 122). METHODS:Cox regression assessed the association between plasma omega-3 and DHA levels and AMD incidence, adjusting for systemic covariates and AMD polygenetic risk score (PRS). Interaction effects of AMD genetic risk (PRS, complement factor H and age-related maculopathy susceptibility 2 genotypes), and plasma omega-3 and DHA levels were tested. For MR analyses, we used random-effect inverse-variance weighted model as primary, with 5 sensitivity models. Causality was considered significant if P < 0.05 in the primary model and at least 2 sensitivity models. MAIN OUTCOME MEASURES:Risk of AMD. RESULTS:Over 12.9 years, 5068 people (1.9%) demonstrated AMD. Higher plasma levels (in millimoles per liter) of omega-3 (hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.72-0.95; P = 0.006) and DHA (HR, 0.65; 95% CI, 0.44-0.96; P = 0.029) were associated with lower risk of receiving an AMD diagnosis. Mendelian randomization showed genetic predisposition to higher plasma omega-3 levels reduced the risk of dry AMD (odds ratio [OR], 0.83; 95% CI, 0.73-0.96; P = 0.010), wet AMD (OR, 0.76; 95% CI, 0.65-0.88; P < 0.001), and any AMD (OR, 0.82; 95% CI, 0.74-0.92; P < 0.001). Similar results were found for plasma DHA levels (wet AMD:OR, 0.79; 95% CI, 0.65-0.96; P = 0.017; any AMD: OR, 0.84; 95% CI, 0.72-0.98; P = 0.030). No significant interaction was found between omega-3 and DHA levels and AMD genetic risk (all P > 0.05). CONCLUSIONS:Both the prospective and MR analyses suggest omega-3 and DHA may protect against AMD, supporting the need for further clinical trials to test their effectiveness in AMD prevention and treatment. FINANCIAL DISCLOSURE(S):Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Creativity is one defining characteristic of human species. There have been mixed findings on how creativity relates to well-being, and little is known about its relationship with career success. We conduct a large-scale genome-wide association study to examine the genetic architecture of occupational creativity, and its genetic correlations with well-being and career success. The SNP-h2 estimates range from 0.08 (for managerial creativity) to 0.22 (for artistic creativity). We record positive genetic correlations between occupational creativity with autism, and positive traits and well-being variables (e.g., physical height, and low levels of neuroticism, BMI, and non-cancer illness). While creativity share positive genetic overlaps with indicators of high career success (i.e., income, occupational status, and job satisfaction), it also has a positive genetic correlation with age at first birth and a negative genetic correlation with number of children, indicating creativity-related genes may reduce reproductive success. A GWAS study reveals that genes related to occupational creativity are associated with both positive and negative well-being variables, positively correlate with career success, and negatively correlate with reproductive success

Introduction: Long axial length (AL) is a risk factor for myopia. Although family studies indicate that AL has an important genetic component with heritability estimates up to 0.94, there have been few reports of AL-associated loci.Methods: Here, we conducted a multiethnic genome-wide association study (GWAS) of AL in 19,420 adults of European, Latino, Asian, and African ancestry from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort, with replication in a subset of the Consortium for Refractive Error and Myopia (CREAM) cohorts of European or Asian ancestry. We further examined the effect of the identified loci on the mean spherical equivalent (MSE) within the GERA cohort. We also performed genome-wide genetic correlation analyses to quantify the genetic overlap between AL and MSE or myopia risk in the GERA European ancestry sample.Results: Our multiethnic GWA analysis of AL identified a total of 16 genomic loci, of which 5 are novel. We found that all AL-associated loci were significantly associated with MSE after Bonferroni correction. We also found that AL was genetically correlated with MSE (rg = −0.83; SE, 0.04; p = 1.95 × 10−89) and myopia (rg = 0.80; SE, 0.05; p = 2.84 × 10−55). Finally, we estimated the array heritability for AL in the GERA European ancestry sample using LD score regression, and found an overall heritability estimate of 0.37 (s.e. = 0.04).Discussion: In this large and multiethnic study, we identified novel loci, associated with AL at a genome-wide significance level, increasing substantially our understanding of the etiology of AL variation. Our results also demonstrate an association between AL-associated loci and MSE and a shared genetic basis between AL and myopia risk.

Purpose: To explore a safe and effective therapy in treating diplopia due to traumatic trochlear nerve palsy. Subjects: Two cases of traumatic trochlear nerve palsy both induced by motorcycle traffic accidents were presented in this study. Both cases were right superior oblique muscle palsy after an accidental head injury affected for more than 6 months (case 1) and 4 years (case 2). Methods of treatment: Both cases were subjected to acupuncture therapy at the acupoint BL1 (Jingming) of both eyes using disposable stainless steel acupuncture needles and were clinically evaluated by the ophthalmologist after each session. Each session extended to 20 minutes, 2 or 3 sessions per week till fully recovered. Result: Clinical symptoms of both cases were significantly improved after 3 sessions and continued the treatment for two more months to consolidate the curative effect due to fear of recurrence of symptoms. Conclusion: Acupuncture can be considered an effective therapy in the treatment of diplopia due to traumatic trochlear nerve palsy in addition to conservative therapy.

Purpose To identify genetic alleles associated with differences in choroidal thickness (CT) in a population-based multiethnic Asian cohort. Methods A population-based multiethnic Asian cohort without retinal pathology was subjected to spectral-domain OCT (SD-OCT) and genotyping of risk alleles in CFH, VIPR2, ARMS2, and CETP. Subfoveal choroidal thickness (SFCT) values were assessed from SD-OCT, and associations with the risk alleles were determined for each cohort. Results A total of 1045 healthy Asian individuals (550 Chinese, 147 Indians, 348 Malays) were prospectively enrolled in the study. Several CFH alleles (rs800292, rs1061170, and rs1329428) were associated with increased SFCT in Indians (+18.7 to +31.7 µm; P = 0.001–0.038) and marginally associated with decreased SFCT in Malays (−12.7 to −20.6 µm; P = 0.014–0.022). Haplotype analysis of CFH revealed variable associations with SFCT among races, with the H6 haplotype being associated with a 29.08-µm reduction in SFCT in the Chinese cohort (P = 0.02) but a 35.2-µm increase in SFCT in the Indian cohort (P < 0.001). Finally, subfield analysis of the Chinese cohort identified associations between the CFH risk allele rs1061170 and reduced CT in the nasal and superior sectors (−20.2 to −25.8 µm; P = 0.003–0.027). Conclusions CFH variants are variably associated with CT among Asian ethnic groups. This has broad implications for the pathogenesis of common diseases such as age-related macular degeneration and central serous choroidopathy, the pathogenesis of which is associated with CT.

INTRODUCTION:In this study, we aimed to compare the performance of a convolutional neural network (CNN)-based deep learning model that was trained on a dataset of normal and abnormal paediatric elbow radiographs with that of paediatric emergency department (ED) physicians on a binomial classification task. METHODS:A total of 1,314 paediatric elbow lateral radiographs (patient mean age 8.2 years) were retrospectively retrieved and classified based on annotation as normal or abnormal (with pathology). They were then randomly partitioned to a development set (993 images); first and second tuning (validation) sets (109 and 100 images, respectively); and a test set (112 images). An artificial intelligence (AI) model was trained on the development set using the EfficientNet B1 network architecture. Its performance on the test set was compared to that of five physicians (inter-rater agreement: fair). Performance of the AI model and the physician group was tested using McNemar test. RESULTS:The accuracy of the AI model on the test set was 80.4% (95% confidence interval [CI] 71.8%-87.3%), and the area under the receiver operating characteristic curve (AUROC) was 0.872 (95% CI 0.831-0.947). The performance of the AI model vs. the physician group on the test set was: sensitivity 79.0% (95% CI: 68.4%-89.5%) vs. 64.9% (95% CI: 52.5%-77.3%; P = 0.088); and specificity 81.8% (95% CI: 71.6%-92.0%) vs. 87.3% (95% CI: 78.5%-96.1%; P = 0.439). CONCLUSION:The AI model showed good AUROC values and higher sensitivity, with the P-value at nominal significance when compared to the clinician group.