It is unclear regarding associations of dietary patterns with a wide range of chronic diseases and which dietary score is more predictive of major chronic diseases. Using the UK Biobank, we examine associations of four individual healthy dietary scores with the risk of 48 individual chronic diseases. Higher Alternate Mediterranean Diet score is associated with a lower risk of 32 (all 8 cardiometabolic disorders, 3 out of 10 types of cancers, 7 out of 10 psychological/neurological disorders, 5 out of 6 digestive disorders, and 9 out of 14 other chronic diseases). Alternate Healthy Eating Index-2010 and Healthful Plant-based Diet Index are inversely associated with the risk of 29 and 23 individual chronic diseases, respectively. A higher Anti-Empirical Dietary Inflammatory Index is associated with a lower risk of 14 individual chronic diseases and a higher incidence of two diseases. Our findings support dietary guidelines for the prevention of most chronic diseases.

Purpose: The purpose of this study was to investigate if education contributes to the risk of myopia because educational activities typically occur indoors or because of other factors, such as prolonged near viewing. Methods: This was a two-sample Mendelian randomization study. Participants were from the UK Biobank, Avon Longitudinal Study of Parents and Children, and Generation R. Genetic variants associated with years spent in education or time spent outdoors were used as instrumental variables. The main outcome measures were: (1) spherical equivalent refractive error attained by adulthood, and (2) risk of an early age-of-onset of spectacle wear (EAOSW), defined as an age-of-onset of 15 years or below. Results: Time spent outdoors was found to have a small genetic component (heritability 9.8%) that tracked from childhood to adulthood. A polygenic score for time outdoors was associated with children's time outdoors; a polygenic score for years spent in education was inversely associated with children's time outdoors. Accounting for the relationship between time spent outdoors and myopia in a multivariable Mendelian randomization analysis reduced the size of the causal effect of more years in education on myopia to −0.17 diopters (D) per additional year of formal education (95% confidence interval [CI] = −0.32 to −0.01) compared with the estimate from a univariable Mendelian randomization analysis of −0.27 D per year (95% CI = −0.41 to −0.13). Comparable results were obtained for the outcome EAOSW. Conclusions: Accounting for the effects of time outdoors reduced the estimated causal effect of education on myopia by 40%. These results suggest about half of the relationship between education and myopia may be mediated by children not being outdoors during schooling.

The metabolic profile predating the onset of Parkinson’s disease (PD) remains unclear. We aim to investigate the metabolites associated with incident and prevalent PD and their predictive values in the UK Biobank participants with metabolomics and genetic data at the baseline. A panel of 249 metabolites was quantified using a nuclear magnetic resonance analytical platform. PD was ascertained by self-reported history, hospital admission records and death registers. Cox proportional hazard models and logistic regression models were used to investigate the associations between metabolites and incident and prevalent PD, respectively. Area under receiver operating characteristics curves (AUC) were used to estimate the predictive values of models for future PD. Among 109,790 participants without PD at the baseline, 639 (0.58%) individuals developed PD after one year from the baseline during a median follow-up period of 12.2 years. Sixty-eight metabolites were associated with incident PD at nominal significance (P < 0.05), spanning lipids, lipid constituent of lipoprotein subclasses and ratios of lipid constituents. After multiple testing corrections (P < 9 $$\times$$× 10⁻⁴), polyunsaturated fatty acids (PUFA) and omega-6 fatty acids remained significantly associated with incident PD, and PUFA was shared by incident and prevalent PD. Additionally, 14 metabolites were exclusively associated with prevalent PD, including amino acids, fatty acids, several lipoprotein subclasses and ratios of lipids. Adding these metabolites to the conventional risk factors yielded a comparable predictive performance to the risk-factor-based model (AUC = 0.766 vs AUC = 0.768, P = 0.145). Our findings suggested metabolic profiles provided additional knowledge to understand different pathways related to PD before and after its onset.

Background: The asymptomatic onset and extremely high mortality rate of aortic aneurysm (AA) highlight the urgency of early detection and timely intervention. The alteration of retinal vascular features (RVFs) can reflect the systemic vascular properties, and be widely used as the biomarker for cardiovascular disease risk prediction. Therefore, we aimed to investigate associations of RVFs with AA and its progression. Methods: In this prospective population-based cohort study, participants with eligible fundus images and without a history of AA at recruitment were included for analysis. A fully automated Retina-based Microvascular Health Assessment System was used to quantify multidimensional RVFs including the branching angle, caliber, complexity, density, length, and tortuosity. Univariable and multivariable Cox regressions were used to estimate the association of RVFs with the incidence of AA and aortic adverse events (AAE). Furthermore, propensity score matching was performed to mitigate the confounding effects of baseline characteristics. Results: During a median follow-up of 11.0 years, 306 incident AA (164 with abdominal AA and 108 with thoracic AA) and 48 incident AAE were documented. In the fully adjusted model, the retinal arterial branching angle (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.77 to 0.99) and the central tendency and variability of minimum venular caliber were significantly associated with the risk of incident AA (HR 1.13-1.15), while the venular minimum angular asymmetry (0.48, 0.30 to 0.77) was significantly associated with the incidence of AAE. Moreover, specific alterations of RVFs were observed in different AA subtypes (caliber in abdominal AA [HR 1.21]; caliber [HR 1.21-1.28], complexity, length, and tortuosity [HR 0.77-0.82] in thoracic AA). Similar results were obtained after propensity score-matched analysis, confirming the stability of these associations. Conclusions: We identified a significant association of certain RVFs with incident AA and AAE, implying that noninvasive, and convenient fundus photography could be a promising tool to facilitate the early detection of AA and subsequent preventative interventions.

The etiology of primary open angle glaucoma is constituted by both intraocular pressure-dependent and intraocular pressure-independent mechanisms. However, GWASs of traits affecting primary open angle glaucoma through mechanisms independent of intraocular pressure remains limited. Here, we address this gap by subtracting the genetic effects of a GWAS for intraocular pressure from a GWAS for primary open angle glaucoma to reveal the genetic contribution to primary open angle glaucoma via intraocular pressure-independent mechanisms. Seventeen independent genome-wide significant SNPs were associated with the intraocular pressure-independent component of primary open angle glaucoma. Of these, 7 are located outside known normal tension glaucoma loci, 11 are located outside known intraocular pressure loci, and 2 are novel primary open angle glaucoma loci. The intraocular pressure-independent genetic component of primary open angle glaucoma is associated with glaucoma endophenotypes, while the intraocular pressure-dependent component is associated with blood pressure and vascular permeability. A genetic risk score for the intraocular pressure-independent component of primary open angle glaucoma is associated with 26 different retinal micro-vascular features, which contrasts with the genetic risk score for the intraocular pressure-dependent component. Increased understanding of these intraocular pressure-dependent and intraocular pressure-independent components provides insights into the pathogenesis of glaucoma.

Background: Implementing lipid control in patients with diabetes is regarded as a potential strategy for halting the advancement of diabetic retinopathy (DR). This study seeks to use Mendelian randomisation (MR) to assess the causal relationship between lipid traits and lipid-lowering drug targets and full-course DR (background DR, severe non-proliferative DR (NPDR) and proliferative DR (PDR)). Methods: A two-sample MR and drug target MR to decipher the causal effects of lipid traits and lipid-lowering drug targets on full-course DR, including background DR, severe NPDR and PDR, was conducted in the study. Genetic variants associated with lipid traits and genes encoding the protein targets of lipid-lowering drugs were extracted from the Global Lipids Genetics Consortium and UK Biobank. Summary-level data of full-course DR are obtained from FinnGen. Results: No significant causal relationship was found between lipid traits and full-course DR. However, in drug target MR analysis, peroxisome proliferator-activated receptor gamma (PPARG) enhancement was associated with lower risks of background DR (OR=0.12, p=0.005) and PDR (OR=0.25, p=0.006). Additionally, mediation MR analysis showed that lowering fasting insulin (p=0.015) and HbA1c (p=0.005) levels mediated most of the association between PPARG and full-course DR. Conclusions: This study reveals PPARG may be a promising drug target for full-course DR. The activation of PPARG could reduce the risk of full-course DR, especially background DR and PDR. The mechanism of the PPARG agonists’ protection of full-course DR may be dependent on the glucose-lowering effect.